Methods, materials and apparatus for treating bone and other tissue

ABSTRACT

A bone cement comprising a first component and a second component, wherein contacting the first component and the second component produces a mixture which attains a high viscosity an initial period and the viscosity of the mixture remains relatively stable for a working time of at least 5 minutes after the initial setting period, and the mixture is suitable for in-vivo use.

RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.11/360,251, filed Feb. 22, 2006, entitled “Methods, Materials andApparatus for Treating Bone and Other Tissue,” which claims the benefitunder 35 USC 119(e) of U.S. provisional applications 60/765,484 filed onFeb. 2, 2006 and entitled “Methods, Materials and Apparatus for TreatingBone and Other Tissue”; 60/762,789 filed on Jan. 26, 2006 and entitled“Methods, Materials and Apparatus for Treating Bone and Other Tissue”;60/763,003, entitled “Cannula” filed on Jan. 26, 2006; U.S. provisionalapplication 60/738,556 filed Nov. 22, 2005 and entitled “Methods,Materials and Apparatus for Treating Bone and Other Tissue”; 60/729,505filed Oct. 25, 2005 and entitled “Methods, Materials and Apparatus forTreating Bone and Other Tissue”; 60/720,725 filed on Sep. 28, 2005 andentitled “Tools and Methods for Treating Bone” and U.S. provisionalapplication No. 60/721,094 filed on Sep. 28, 2005 and entitled “Toolsand Methods for Material Delivery into the Body”. The disclosures ofthese applications are incorporated herein by reference.

The present application is also a Continuation-in-Part of U.S. Ser. No.11/194,411, filed Aug. 1, 2005 which claimed priority from IL 166017filed Dec. 28, 2004 and IL 160987 filed Mar. 21, 2004 and also claimedthe benefit under 35 USC 119(e) of U.S. Provisional Application No.60/647,784 filed on Jan. 31, 2005 and U.S. Provisional Application No.60/592,149 filed on Jul. 30, 2004. The present application is also aContinuation-in Part of PCT/IL2005/00812 of Jul. 31, 2005. The presentapplication also claims the benefit under 35 USC 119(e) of U.S.provisional application No. 60/654,495 filed Feb. 22, 2005. Thedisclosures of these applications are incorporated herein by reference.

This application is related to PCT Application No. PCT/IL2004/000527filed on Jun. 17, 2004, Israel Application No. 160987 filed on Mar. 21,2004, U.S. Provisional Applications: 60/478,841 filed on Jun. 17, 2003;60/529,612 filed on Dec. 16, 2003; 60/534,377 filed on Jan. 6, 2004 and60/554,558 filed on Mar. 18, 2004; U.S. application Ser. No. 09/890,172filed on Jul. 25, 2001, and U.S. application Ser. No. 09/890,318 filedon Jul. 25, 2001. The disclosures of all of these applications areincorporated herein by reference.

This application is also related to U.S. application Ser. No. 10/549,409entitled “Hydraulic Device for the injection of Bone Cement inPercutaneous Vertebroplasty filed on Sep. 14, 2005, the disclosure ofwhich is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to viscous materials, methods forinjection of a viscous material into a living subject and/or to deliverysystems for said injection.

BACKGROUND OF THE INVENTION

A common occurrence in older persons is compression fractures of thevertebrae, causing both pain and a shortening (or other distortion) ofstature. One common treatment is vertebroplasty, in which cement isinjected into a fractured vertebra. While this treatment fixes thefracture and reduces pain, it does not restore the vertebra and personto their original height. Another problem is that the cement is injectedin a liquid phase so that it may be unintentionally injected outside ofthe vertebra and/or may migrate out through cracks in the vertebra. Thismay cause considerable bodily harm.

Another common treatment is kyphoplasty, in which the fracture isreduced, for example by first inflating a balloon inside the vertebraand then injecting a fixing material and/or an implant. The problem ofcement migration is reduced, but not avoided, as a lower pressure can beused to inject the cement.

In general, polymeric cements becomes more viscous as the polymer chaingrows by reacting directly with the double bond of a monomer.Polymerization begins by the “addition mechanism” in which a monomerbecomes unstable by reacting with an initiator, a volatile molecule thatis most commonly a radical (molecules that contain a single unpairedelectron). Radicals bond with monomers, forming monomer radicals thatcan attack the double bond of the next monomer to propagate the polymerchain. Because radicals are so transient, initiators are often added inthe form of an unreactive peroxide form that which is stable insolution. Radicals are formed when heat or light cleaves the peroxidemolecule. For applications in which high temperatures are not practical(such as the use of bone cement in vivo), peroxide is cleaved by addinga chemical activator such as N,N-dimethyl-p-toluidine. (Nussbaum DA etal: “The Chemistry of Acrylic Bone Cement and Implication for ClinicalUse in Image-guided Therapy”, J Vasc Intery Radiol (2004); 15:121-126;the content of which is fully incorporated herein by reference).

Viscous cement is advantageous not only in reducing the risk of itsleakage, but also, because of its ability to infiltrate into theintravertebral cancellous bone (interdigitaion) [see G Baroud et al,Injection biomechanics of bone cements used in vertebroplasty,Bio-Medical Materials and Engineering 00 (2004) 1-18]. Baroud alsosuggests that about 95% of the applied injection pressure is required toovercome friction in the cannula. In addition, viscous material mayreduce the fracture.

Examples of commercially available viscous bone cements include, but arenot limited to, CMW® Nos. 1, 2 and 3 (DePuy Orthopaedics Inc.; Warsaw,Ind., USA) and Simplex™-P and -RO (Stryker Orthopaedics; Mahwah, N.J.,USA). These cements are characterized by a liquid phase after mixing andprior to achieving a viscosity of 500 Pascal second. In a typical usescenario, these previously available cements are poured, while in aliquid phase, into a delivery device.

There have also been attempts to reduce cement migration by injectingmore viscous cement, for example, during the doughing time and thebeginning of polymerization. However, the injection methods suggestedrequire higher pressures for the more viscous material. Also, some typesof viscous materials, such as hardening PMMA, have a small workabilitywindow at high viscosities, as they harden very quickly once they reacha high viscosity. This has generally prevented very viscous materialsand the associated very high pressures from being used. One possiblereason is that as pressures increase, the physician is prevented fromreceiving feedback on the resistance of the body to the injection of thecement. Thus, over-injection can easily occur.

Some fixing materials, such as polymethylmethacrylate (PMMA), emit heatand possibly toxic materials while setting. These may further weaken thebone and possibly cause the cement to loosen and/or the bone tofracture.

It has recently been suggested that some fixing materials, being harderthan bone, induce fractures in nearby bones.

It is also known to use bone-like repair materials, such as a slurry ofbone chips, which apparently do not induce such fractures. However,injecting such materials is difficult due to their viscosity.

US patents and applications U.S. Pat. Nos. 4,969,888, 5,108,404,6,383,188, 2003/0109883, 2002/0068974, U.S. Pat. Nos. 6,348,055,6,383,190, 4,494,535, 4,653,489 and 4,653,487, the disclosures of whichare incorporated herein by reference describe various tools and methodsfor treating bone.

An additional manner to deliver bone cement into the vertebra is using atamping instrument (U.S. Pat. Nos. 6,241,734 and 6,613,054), comprisinga cannula and a rod, which urges the material within the cannula intothe bone.

US patent application 20040260303, the disclosure of which isincorporated herein by reference, teaches an apparatus for deliveringbone cement into a vertebra.

Cannulae with working sleeves are describe, for example, in U.S. Pat.Nos. 6,241,734 and 6,613,054, the disclosures of which are fullyincorporated herein by reference.

SUMMARY OF THE INVENTION

An aspect of some embodiments of the invention relates to formulationsof bone cement which provide a window of time during which the cement issuitably viscous for injection. In an exemplary embodiment of theinvention, the cement achieves a high viscosity rapidly when componentsare mixed and then sets slowly. In an exemplary embodiment of theinvention, the cement remains viscous when held above a thresholdtemperature and sets when cooled below the threshold temperature. In anexemplary embodiment of the invention, the cement is a non-settingcement. Optionally, there is no liquid phase when cement components aremixed.

An aspect of some embodiments of the invention relates to a viscous bonecement which has an enhanced high-viscosity window before it sets andwhere viscosity, while high, does not vary to a degree which influencesinjection parameters. Optionally, the viscosity in the window is 500,optionally 1,000, optionally 1,500, optionally 2,000 Pascal-sec orlesser or greater or intermediate values. Optionally, the cement issufficiently viscous to move fractured bone, such as vertebral plates ofa collapsed vertebra, as it is injected. In an exemplary embodiment ofthe invention, injection of viscous cement contributes to fracturereduction and/or restoration of vertebral height.

In an exemplary embodiment of the invention, mixture of polymer andmonomer components produces a high viscosity material within 1 second,within 5 seconds, within 10 seconds, within 15 seconds, within 30seconds, within 60 seconds, within 120 seconds or intermediate times.Optionally, once a high viscosity is achieved, the viscosity remainsstable for 5 minutes or more. In an exemplary embodiment of theinvention, this interval of stable viscosity provides a window ofopportunity for performance of a medical procedure.

In an exemplary embodiment of the invention, the working window is atleast 3 minutes, optionally at least 5 minutes, optionally at least 8minutes, optionally at least 10 minutes, optionally at least 15 minutes,optionally at least 20 minutes. In an exemplary embodiment of theinvention, increased viscosity is provided a short time after mixing ofthe cement, for example, zero time (for a pre-provided viscousmaterial), less than 1 minutes or less than 2 or less than 3 minutesafter mixing is complete.

In an exemplary embodiment of the invention, the cement may include anacrylic polymer, such as polymethylmethacrylate (PMMA) and/or styrene.In an exemplary embodiment of the invention, polymer bead size and/ormolecular weight of the polymer prior to polymerization contribute to afinal viscosity of the mixture. Optionally, an average molecular weightof the acrylic polymer is in excess of 60,000, optionally 70,000,optionally 80,000, optionally 90,000, optionally 100,000 Dalton. In anexemplary embodiment of the invention, the average molecular weight ofthe acrylic polymer in the beads is in the range of about 100,000 to120,000, optionally about 110,000 Dalton. Optionally, the molecularweight of a portion of the acrylic polymer in the beads has a highmolecular weight. Optionally, the portion includes 0.25%, 0.5%, 1%, 2%,3% or lesser or intermediate or greater percentages of the total acrylicpolymer in the beads. Optionally, high molecular weight acrylic polymerin the beads is 600,000, optionally 900,000, optionally 1,100,000 Daltonor intermediate or lesser or greater values. In an exemplary embodimentof the invention, approximately 1% of the PMMA in the beads ischaracterized by a molecular weight of 700,000 to 1,000,000 Dalton andthe average molecular weight of the PMMA is approximately 110,000Dalton. In an exemplary embodiment of the invention, bead diameter is inthe range of was in the range of 10-200 microns, optionally, 20 to 150microns, optionally with an average of about 60 microns or lesser orintermediate or greater sizes.

An aspect of some embodiments of the invention relates to the use ofmaterial that has a glass transition temperature higher than 37 degreesCelsius as a bone cement. In an exemplary embodiment of the invention,heating the material above the glass transition temperature transformsthe material to a dough-like or putty-like state. Optionally, Dough-likeindicates a viscosity of at least 500, optionally at least 900,optionally at least 1000 Pascal seconds or lesser or intermediate orgreater values. In an exemplary embodiment of the invention, thedough-like state is characterized in that a pressure less than 200atmospheres is sufficient to cause it to flow through a tube with an IDof 3 mm and a length of 100 mm. Optionally, the dough-like material issuitable for delivery using a high-pressure fluid delivery system, forexample as disclosed herein. In an exemplary embodiment of theinvention, the temperature is lower than a maximum temperature allowedinside the human body, for example, being below 60 degrees Celsius,below, 50 degrees, 45 and/or below 40 degrees or intermediate or lessertemperatures. In an exemplary embodiment of the invention, a penetratingtube is subject to temperature control, for example by means ofinsulation. Optionally, a double-walled tube with vacuum pressurebetween its walls provides the isolation.

In an exemplary embodiment of the invention, the material (e.g., bonecement) includes processed bone (from human or animals origin) and/orsynthetic bone. Optionally, the cement has osteoconductive and/orosteoinductive behavior.

In an exemplary embodiment of the invention, a bone cement is injectedinto a bone void as a preventive therapy or as a treatment for anexisting condition.

In some exemplary embodiments of the invention, a temperature controlunit is provided to facilitate heating and/or cooling of bone cement.Optionally, temperature control is applied to increase the handlingand/or working time (e.g., heat may be applied to offset temperaturechanges resulting from high pressures). In various exemplary embodimentsof the invention, the temperature control unit operates on cement in anexternal reservoir and/or cement in a delivery system reservoir.

An aspect of some embodiments of the invention relates to hydraulicsystems for delivering viscous material into a bone. Optionally,delivery is via a small diameter tube such as a bone access cannula. Inan exemplary embodiment of the invention, delivery is via a tube with aninner diameter of 1.5 mm, 2 mm, 3 mm, 4 mm or lesser or greater orintermediate values. In an exemplary embodiment of the invention, thesystem is operable by foot and/or is battery powered. In an exemplaryembodiment of the invention, the system provides sufficient pressure todeliver at least 5 ml, optionally at least 10 ml, of a viscous bonecement as a single continuous aliquot.

In an exemplary embodiment of the invention, the system design assuresthe physician's hands are located outside an X-ray radiation zone. In anexemplary embodiment of the invention, a hand operable actuator for apressure source is located 20 cm, 40 cm, 60 cm, 100 cm or intermediateor greater distances from a cement reservoir.

In an exemplary embodiment of the invention, the actuator for thepressure source employs a threaded steel rod which passes through aplastic nut. Optionally, this combination of materials reduces thefriction coefficient. Optionally, reducing a diameter of the boltreduces a radius-of-friction. Optionally, reducing a radius-of-frictionreduces an applied moment. In an exemplary embodiment of the invention,a short actuation handle permits an operator to grasp the handle on bothsides of the axis (bolt) so that moment is applied without generatingundesired radial force.

In an exemplary embodiment of the invention, the pressure sourceincludes a safety valve. In an exemplary embodiment of the invention,solidification of the cement contributes to increased pressure.Optionally, solidification of the cement increases pressure to athreshold which operates the safety valve. In an exemplary embodiment ofthe invention, the threshold is significantly below a maximum internalpressure which the system can withstand.

In an exemplary embodiment of the invention, the cement reservoirincludes a floating piston. Optionally, the floating piston separatesbetween cement and a hydraulic fluid. In an exemplary embodiment of theinvention, the cement reservoir includes a piston mounted on a rod.

In various exemplary embodiments of the invention, the hydraulicactuator is operable by various means. Optionally, the pressure sourceincludes a foot operable actuator. In an exemplary embodiment of theinvention, the foot operable actuator includes a clutch plate with ahole with a varying aspect ration. In an exemplary embodiment of theinvention, the pressure source provides a pressure of 50, optionally100, optionally 150, optionally 200, optionally 300 atmospheres orlesser or greater or intermediate values. Optionally, the hydraulicactuator provides pressure amplification. In an exemplary embodiment ofthe invention, pressure amplification is provided by mechanicaladvantage (levers) and/or bolt thread step and/or a hydraulicamplification.

In an exemplary embodiment of the invention, mated threaded materialsare chosen to reduce the friction coefficient (μ). Optionally, thefriction coefficient is 0.2 or less. Optionally, this frictioncoefficient increase maneuverability. Optionally, a cover serves as anut and is made of a polymer/plastic. Optionally, a drive shaft servesas a bolt and is made of steel. Optionally, a Radius of Friction (R;bolt radius in this example) is reduced by reducing the thread diameterof the bolt and nut. In an exemplary embodiment of the invention, R is2, optionally 3, optionally 4, optionally 5 mm or intermediate values.

According to various embodiments of the invention, the cannula may beequipped with one or more apertures for cement delivery at a distal endand/or near the distal end. In an exemplary embodiment of the invention,lateral openings on the cannula permit sideways injection to a desiredtarget in a bone.

An aspect of some embodiments of the invention relates to an apparatusfor mixing materials using a revolving paddle which does not rotate.Optionally, the paddle provides high shearing forces. Optionally, cementis easily removable from a flat paddle. Optionally, the mixer includes adelivery mechanism adapted to facilitate delivery of a viscous mixturefrom the mixer to an external reservoir. Optionally, the paddle pressesmaterials against a wall of a container.

An aspect of some embodiment of the invention relates to the use of ahigh-pressure delivery system to fill a small diameter cannula with ahigh viscosity material. In an exemplary embodiment of the invention,pressure to fill the cannula is provided by a hydraulic delivery system.Optionally, once the cannula is filled, the cement may be injected intothe body in various means, for example, using a tamping instrumentincluding a rod adapted to comply with a lumen of the cannula. In anexemplary embodiment of the invention, pressure to fill the cannula isprovided by a piston with a diameter greater than the cannula lumen. Inan exemplary embodiment of the invention, a plurality of cannulae arepre-filled and used as needed. Optionally, the cannulae are providedinto the body through an outer sheath which remains in place when thecannulae are changed. Alternatively or additionally, the cannula isrefilled while inside the body.

An aspect of some embodiments of the invention relates to a bone cementcannula with a permanently closed distal tip. Optionally, delivery ofcement is through one or more apertures on a lateral surface of thecannula near the distal tip. In an exemplary embodiment of theinvention, an orientation marking on a proximal portion of the cannulafacilitates correct orientation of the lateral aperture(s) after thedistal tip of the cannula is inserted. Optionally, the cannula includesa depth marking or coining.

In an exemplary embodiment of the invention, the closed tip is used as atrocar tip for penetrating tissue and/or bone. Alternatively oradditionally, the closed tip is used to aim cement delivery.

In an exemplary embodiment of the invention, there is provided a bonecement comprising:

a first component; and

a second component,

wherein, contacting the first component and the second componentproduces a mixture which attains a viscosity greater than 500 Pascalseconds within an initial setting period,

wherein the viscosity of the mixture remains between 500 and 2000 Pascalseconds for a working time of at least 5 minutes after the initialsetting period, and

wherein the mixture is suitable for in-vivo use.

Optionally, the working time is at least 8 minutes long.

Optionally, the initial setting period is less than 3 minutes.

Optionally, the initial setting period does not exceed 1 minutes.

Optionally, the mixture solidifies after the working time.

Optionally, the initial setting period is less than 3 minutes and themixture solidifies after the working time.

Optionally, the first component includes PMMA and Barium Sulfate.

Optionally, the second component includes MMA and DMPT.

Optionally, the first component includes PMMA, Barium Sulfate, andBenzoyl Peroxide, and wherein the second component includes MMA, DMPT,and Hydroquinone.

Optionally, the viscosity of greater than 500 Pascal-second results atleast partly from a polymerization reaction.

In an exemplary embodiment of the invention, there is provided a bonecement comprising:

a first component; and

a second component,

wherein, contacting the first component and the second componentproduces a mixture which attains a viscosity greater than 200 Pascalseconds within 1 minute,

wherein the viscosity of the mixture remains between 200 and 2000 Pascalseconds for a working time of at least 5 minutes after the initialsetting period,

wherein the viscosity of said cement is changing by less than 10% in aperiod of 2 minutes within said working time, and

wherein the mixture is suitable for in-vivo use.

In an exemplary embodiment of the invention, there is provided a bonecement comprising:

a mixture resulting from the contacting of a first component includingPMMA with a second component including MMA,

wherein a porton of the PMMA has a molecular weight between about600,000 Dalton and about 1,200,000 Dalton.

Optionally, the first component contains about 69.4% w/w PMMA, about30.1% Barium Sulfate, and about 0.5% Benzoyl Peroxide; and wherein thesecond component contains about 98.5% v/v MMA, about 1.5% DMPT, andabout 20 ppm Hydroquinone.

Optionally, the average molecular weight of the PMMA is between about80,000 Dalton and about 180,000 Dalton.

Optionally, the average molecular weight of the PMMA is about 110,000Dalton.

Optionally, at least 80% of the PMMA has a bead size between 10 and 200microns.

Optionally, the cement further comprises processed bone and/or syntheticbone that is mixed together with the first component and the secondcomponent.

In an exemplary embodiment of the invention, there is provided a bonecement kit comprising:

a first component including PMMA and a second component including MMA,

wherein a porton of the PMMA has a molecular weight between about600,000 Dalton and about 1,200,000 Dalton.

Optionally, the first component includes about 69.4% w/w PMMA, about30.1% Barium Sulfate, and about 0.5% Benzoyl Peroxide; and

the second component including about 98.5% v/v MMA, about 1.5% DMPT, andabout 20 ppm Hydroquinone.

Optionally, the average molecular weight of the PMMA is between about80,000 Dalton and about 180,000 Dalton.

Optionally, the average molecular weight of the PMMA is about 110,000Dalton.

Optionally, at least 80% of the PMMA has a bead size between 10 and 200microns.

In an exemplary embodiment of the invention, there is provided avertebral implant comprising:

a quantity of cement characterized by a viscosity between 500 and 2000Pascal seconds for at least 5 minutes, the cement injectable into avertebral body during the at least 5 minutes, and capable of subsequenthardening therein.

Optionally, the at least 5 minutes is at least 8 minutes.

Optionally, the quantity of cement is at least 1 ml.

In an exemplary embodiment of the invention, there is provided anapparatus for injecting bone cement comprising:

a reservoir configured to hold at least 5 ml of unhardened bone cement,the reservoir having an outlet; and

a hydraulically driven plunger configured to press the cement in thereservoir against the outlet with an internal pressure of at least 40atm, so that at least a portion of the cement will be forced out of thereservoir through the outlet;

wherein the reservoir and the plunger are configured to withstand theinternal pressure.

Optionally, the apparatus comprises a cannula configured to route thecement that is forced out of the outlet into a bone in a living subject.

Optionally, the pressure to operate the hydraulically driven plunger isgenerated by a hydraulic pressure source that is located at least 25 cmaway from the plunger, and wherein the hydraulic pressure source has anactuator.

Optionally, each actuation of the actuator by a user causes the plungerto force a predetermined amount of cement out of the reservoir.

Optionally, the predetermined amount is between 0.15 and 0.5 ml.

Optionally, pressure to operate the hydraulically driven plunger isgenerated by a hydraulic pressure source including a foot-operableactuator.

Optionally, each actuation of the foot-operable actuator by a usercauses the plunger to force a predetermined amount of cement out of thereservoir.

Optionally, the cannula has an inner diameter not exceeding 2.5 mm and alength of at least 100 mm.

Optionally, at least part of the reservoir is made of amorphous nylon.

Optionally, at least part of the reservoir is transparent.

Optionally, the reservoir is configured to hold at least 10 ml ofcement.

Optionally, the internal pressure is at least 100 atm.

Optionally, the internal pressure is at least 200 atm.

In an exemplary embodiment of the invention, there is provided a methodof delivering unhardened cement from a reservoir into a bone via acannula, the cannula having an inlet and an outlet, the methodcomprising:

hydraulically generating a pressure of at least 40 atm in response to anactuation input; and

using the pressure to force at least 5 ml of the cement out of thereservoir into the inlet of the cannula after the outlet of the cannulahas been positioned in a desired location in the bone.

Optionally, the pressure is generated by a hydraulic pressure sourcethat is located at least 25 cm away from the reservoir, and wherein theinput originates from an actuator for the hydraulic pressure source.

Optionally, each actuation of the actuator by a user causes apredetermined amount of cement to be forced out of the reservoir.

Optionally, the predetermined amount is between 0.15 and 0.5 ml.

Optionally, the input originates from a foot-operable actuator for thehydraulic pressure source.

Optionally, each actuation of the foot-operable actuator by a usercauses a predetermined amount of cement to be forced out of thereservoir.

Optionally, the pressure is at least 100 atm.

Optionally, the pressure is at least 200 atm.

In an exemplary embodiment of the invention, there is provided anapparatus for injecting bone cement comprising:

a reservoir configured to hold at least 5 ml of a bone cement having aviscosity of at least 900 Pascal seconds, the reservoir having anoutlet; and

a hydraulically actuated plunger configured to press the cement in thereservoir against the outlet with enough pressure to force at least someof the cement out of the reservoir in response to an actuation input.

Optionally, the apparatus comprises a cannula operatively configured toroute cement from the outlet into a bone in a living subject.

Optionally, the pressure for operating the hydraulically actuatedplunger is generated by a hydraulic pressure source located at least 25cm away from the plunger.

Optionally, each actuation of the actuator by a user causes the plungerto force a predetermined amount of cement out of the reservoir.

Optionally, the predetermined amount is between 0.15 and 0.5 ml.

Optionally, the pressure for operating the hydraulically actuatedplunger is generated by a hydraulic pressure source actuatable by afoot-operable actuator.

Optionally, each actuation of the foot-operable actuator by a usercauses the plunger to force a predetermined amount of cement out of thereservoir.

Optionally, at least part of the reservoir is made of amorphous nylon.

Optionally, at least part of the reservoir is transparent.

Optionally, the reservoir is configured to hold at least 10 ml ofcement.

In an exemplary embodiment of the invention, there is provided a methodof flowing a viscous cement from a reservoir into a bone via a cannula,the method comprising:

generating a pressure within a cement having a viscosity of at least 900Pascal seconds and residing in a reservoir in response to an actuationinput;

wherein the pressure is generated using hydraulics and forces at leastsome of the cement out of the reservoir through an outlet.

Optionally, the pressure forces at least 5 ml of the cement into theinlet of a cannula operably connected to the outlet of the reservoirafter a distal tip of the cannula has been positioned in a desiredlocation in the bone.

Optionally, the pressure is generated by a hydraulic pressure sourcethat is located at least 25 cm away from the reservoir.

Optionally, each actuation input causes a predetermined amount of cementto be forced out of the reservoir.

Optionally, the predetermined amount is between 0.15 and 0.5 ml.

Optionally, the pressure is generated by a hydraulic pressure sourcecomprising a foot-operable actuator.

Optionally, each actuation of the foot-operable actuator causes apredetermined amount of cement to be forced out of the reservoir.

In an exemplary embodiment of the invention, there is provided a bonecement comprising:

a biocompatible material having a glass transition temperature above 37degrees

Celsius, wherein the biocompatible material is injectable into a bonewhen heated above its glass transition temperature.

Optionally, the material comprises polycaprolactone.

Optionally, the material comprises Polylactic acid (PLA).

Optionally, the material also includes ground bone.

In an exemplary embodiment of the invention, there is provided avertebral implant comprising:

a quantity of a cement comprising a material having a glass transitiontemperature above 37 degrees Celsius, the cement injectable into avertebral body so long as it remains at a temperature above the glasstransition temperature, and capable of hardening within the vertebralbody after injection therein and subsequent cooling.

Optionally, the cement is bioabsorbable.

Optionally, the cement also contains ground bone.

Optionally, the material comprises polycaprolactone.

Optionally, the material comprises Polylactic acid (PLA).

In an exemplary embodiment of the invention, there is provided anintra-medular nail comprising:

a quantity of a cement comprising a material having a glass transitiontemperature above 37 degrees Celsius, the cement injectable into amedullary canal of a long bone so long as it remains at a temperatureabove the glass transition temperature, and capable of hardening withinthe canal after injection therein and subsequent cooling.

Optionally, the cement is bioabsorbable.

Optionally, the cement also contains ground bone.

Optionally, the material comprises polycaprolactone.

Optionally, the material comprises Polylactic acid (PLA).

In an exemplary embodiment of the invention, there is provided a methodof injecting bone cement, the method comprising:

-   (a) retaining a cement characterized by a viscosity of at least 500    Pascal-second within a reservoir; and-   (b) applying sufficient pressure to the cement in the reservoir to    propel at least 5 ml of the material from the reservoir through a    bone injection cannula operably connected to an outlet of the    reservoir and having a distal tip inserted in a bone, the cannula    characterized by an internal diameter not exceeding 4 mm.

In an exemplary embodiment of the invention, there is provided a methodof injecting bone cement, the method comprising:

-   (a) retaining a cement characterized by a viscosity which requires a    pressure of at least 20 atmosphere to cause the cement to flow    through a cannula operably connected to an outlet of the reservoir    and having a distal tip inserted in a bone and characterized by an    internal diameter not exceeding 2.5 mm and by a length of at least    100 mm within a reservoir; and-   (b) applying the pressure.

In an exemplary embodiment of the invention, there is provided a cementcomprising an acrylic polymer mixture, the cement achieving a viscosityof at least 500 Pascal-second within 180 seconds following initiation ofmixing of a monomer component and a polymer component and characterizedby sufficient biocompatability to permit injection into bone.

In an exemplary embodiment of the invention, there is provided a methodof treating a bone, the method comprising:

delivering a bone cement which achieves a viscosity of at least 500Pascal-second within 160 seconds from a time at which a polymercomponent and a monomer component of the cement are contacted one withanother into a bone.

In an exemplary embodiment of the invention, there is provided a systemfor delivery of a viscous material into a bone, the system comprising:

-   (a) a reservoir containing a volume of a material characterized by a    viscosity of at least 900 Pascal-second and operably connected to a    pressure source;-   (b) the pressure source adapted to apply sufficient pressure to the    material in the reservoir by advancement of a piston within the    reservoir to expel at least 5 ml of the material from the reservoir    without retraction of the piston;-   (c) an actuator operable to activate the pressure source; and-   (d) a tube adapted to deliver said pressure from said pressure    source to said reservoir.

In an exemplary embodiment of the invention, there is provided anapparatus for mixing, the apparatus comprising:

-   (a) a container adapted to contain at least a polymer component and    a monomer component of a bone cement to be mixed;-   (b) a mixing paddle attachable to a drive mechanism via a mixing    element axle; and-   (c) the drive mechanism adapted to move the mixing paddle along a    travel path in the mixing container so that a reference point on the    mixing element will face in a same direction at every point on the    travel path.

In an exemplary embodiment of the invention, there is provided a methodof treating a bone comprising introducing a material with a glasstransition temperature above 37 degrees Celsius when the material isabove the glass transition temperature.

In an exemplary embodiment of the invention, there is provided a use ofa material with a glass transition temperature above 37 degrees Celsiusin formulation of a bone cement.

In an exemplary embodiment of the invention, there is provided a methodfor treating vertebra, the method comprising:

-   (a) heating a bone cement including a material with a glass    transition temperature above 37 degrees Celsius at least to its    glass transition temperature; and-   (b) flowing the bone cement into an interior of a vertebra while the    material remains at least at the glass transition temperature.

In an exemplary embodiment of the invention, there is provided a methodfor treating long bones, the method comprising:

-   (a) heating a bone cement including a material with a glass    transition temperature above 37 degrees Celsius at least to its    glass transition temperature; and-   (b) flowing the bone cement into an interior of a medullary canal of    a long bone while the material remains at least at the glass    transition temperature.

In an exemplary embodiment of the invention, there is provided a bonecement delivery cannula, the cannula comprising:

-   (a) an inner lumen adapted to provide a channel of fluid    communication between a bone cement reservoir and at least one    lateral cement ejection aperture; and-   (b) a permanently axially closed distal tip.

In an exemplary embodiment of the invention, there is provided a methodof delivering bone cement to a bone, the method comprising:

flowing bone cement through an inner lumen of a cannula characterized bya permanently axially closed distal tip so that the cement exits atleast one lateral aperture of the cannula.

In an exemplary embodiment of the invention, there is provided anapparatus for filling an injection reservoir with a viscous material,the apparatus comprising:

-   (a) a container capable of containing a viscous material;-   (b) a transfer piston insertable in the container so that the piston    forms a circumferential seal with respect to the container, the    transfer piston including a hole; and-   (c) a mechanism for attaching an aperture of an injection reservoir    to the hole in the transfer piston.

In an exemplary embodiment of the invention, there is provided aninjection kit, the kit comprising:

a sterile package containing

-   (a) a hydraulic pressure source capable of delivering at least 50    atmospheres of pressure to an injection reservoir;-   (b) a quantity of a fluid contained in the pressure source; and-   (c) a connector adapted for connection to an injection reservoir.

In an exemplary embodiment of the invention, there is provided a methodof restoring a height of a subject, the method comprising:

flowing a sufficient quantity of a material characterized by a viscosityof at least 500 Pascal second at the time of injection through a cannulacharacterized by an ejection port located within a vertebra to at leastpartially reduce a vertebral fracture.

In an exemplary embodiment of the invention, there is provided a systemfor injection of material into a bone, the system comprising:

-   (a) a reservoir containing material to be injected into a bone, said    reservoir deployed external to a body of a subject;-   (b) a pressure source adapted to apply sufficient pressure to the    material in the reservoir to expel at least a portion of the    material from the reservoir through a cannula;-   (c) an actuator operable to activate the pressure source; and-   (d) the cannula adapted for insertion into the bone, said cannula    connectable to the external reservoir;

wherein an operator of the system may perform an injection touching onlythe actuator.

In an exemplary embodiment of the invention, there is provided a bonecement comprising an acrylic polymer mixture, the cement achieving aviscosity of at least 500 Pascal-second when 100% of a polymer componentis wetted by a monomer component.

Optionally, the cement achieves a viscosity of at least 500Pascal-second when 95% of a polymer component is wetted by a monomercomponent.

In an exemplary embodiment of the invention, there is provided a bonecement comprising:

a monomer containing component and a polymer containing component, thecement characterized in that when the monomer containing component andthe polymer containing component contact one another so that the polymercomponent is wetted by the monomer component a high viscosity cementcharacterized by a relatively stable flowability for a period of atleast 8 minutes results after an initial setting period.

In an exemplary embodiment of the invention, there is provided a bonecement according to claim 95, wherein the initial setting period doesnot exceed 2 minutes.

Optionally, the initial setting period does not exceed 0.5 minutes.

Optionally, the initial setting period does not exceed 5 seconds.

Optionally, the high viscosity is at least 500 Pascal sec.

Optionally, the high viscosity is at least 900 Pascal sec.

Optionally, the stable flowability results from a change in viscosity ofless than 200 Pascal sec.

In an exemplary embodiment of the invention, there is provided a bonecement comprising a monomer containing a monomer component and a polymercontaining component, the cement characterized in that when the monomercontaining component and the polymer containing component contact oneanother so that the polymer component is wetted by the monomer componenta high viscosity cement is formed after an initial setting period, aviscosity of said high viscosity cement changing by less than 20% in aperiod of 5 minutes.

Optionally, the initial setting period does not exceed 2 minutes.

Optionally, the initial setting period does not exceed 0.5 minutes.

Optionally, the initial setting period does not exceed 5 seconds.

Optionally, the high viscosity is at least 500 Pascal sec.

Optionally, the high viscosity is at least 900 Pascal sec.

Optionally, the stable flowability results from a change in viscosity ofless than 200 Pascal sec.

Optionally, the cement achieving a viscosity of at least 500Pascal-second within 180 seconds following initial contact of a monomercomponent and a polymer component.

Optionally, the viscosity is at least 900 Pascal sec.

Optionally, the viscosity is at least 1500 Pascal sec.

Optionally, the viscosity is achieved within 2 minutes.

Optionally, the viscosity is achieved within 1 minute.

Optionally, the viscosity is achieved within 45 seconds.

In an exemplary embodiment of the invention, there is provided a bonecement, the cement achieving a putty like state when 95% of a polymercomponent is wetted by a monomer component.

Optionally, the putty like state is characterized by a viscosity of atleast 500 Pascal sec.

Optionally, the putty like state is characterized by a viscosity of atleast 900 Pascal sec.

Optionally, the 95% wetting occurs within 60 seconds of initial contact.

In an exemplary embodiment of the invention, there is provided a methodof injecting bone cement, the method comprising:

-   (a) providing a reservoir containing a cement characterized by a    viscosity of at least 500 Pascal-second; and-   (b) applying sufficient pressure to the cement in the reservoir to    propel at least 5 ml of the material from the reservoir through a    bone injection cannula characterized by an internal diameter not    exceeding 4 mm.

Optionally, providing includes mixing components so that they achieve aviscosity of at least 500 Pascal-second within 160 seconds from thebeginning of mixing to form a viscous cement.

Optionally, mixing occurs in the reservoir.

Optionally, providing includes use of a non-setting cement characterizedby a viscosity of at least 500 Pascal-second.

Optionally, the at least 5 ml flows through the cannula as anuninterrupted aliquot.

Optionally, the mixing occurs in a separate container and providingincludes a transfer to the reservoir, the transfer performed after thecement reaches the viscosity of at least 500 Pascal-second.

Optionally, mixing components causes the cement to achieve a viscosityof at least 900 Pascal-second within 160 seconds from the beginning ofmixing.

Optionally, the method includes introducing the cannula into an interiorof a bone.

Optionally, said bone is a vertebra.

Optionally, said cannula is introduced into the bone via a workingsleeve, the working sleeve having an inner diameter slightly larger thanan outer diameter of the cannula.

In an exemplary embodiment of the invention, there is provided a methodof injecting bone cement, the method comprising:

-   (a) providing a reservoir containing a cement characterized by a    viscosity which requires a pressure of at least 20 atmosphere to    cause the cement to flow through a cannula characterized by an    internal diameter not exceeding 2.5 mm and by a length of at least    100 mm;-   (b) applying the pressure.

Optionally, the applying the pressure begins within 60 seconds of aninitiation of mixing of components of the cement.

Optionally, the applying the pressure begins within 120 seconds of aninitiation of mixing of components of the cement.

Optionally, the applying the pressure begins within 180 seconds of aninitiation of mixing of components of the cement.

In an exemplary embodiment of the invention, there is provided a bonecement comprising an acrylic polymer mixture, the cement achieving aviscosity of at least 500 Pascal-second within 180 seconds followinginitiation of mixing of a monomer component and a polymer component.

Optionally, the viscosity of at least 500 Pascal-second results at leastpartly from a polymerization reaction.

Optionally, the viscosity of at least 500 Pascal-second results at leastpartly from particles characterized by a large surface area provided inthe cement.

Optionally, said particles characterized by a large surface area includeZirconium.

Optionally, said particles characterized by a large surface area includebone.

Optionally, said cement achieves the viscosity of at least 500Pascal-second without passing through an apparent liquid phase.

Optionally, the cement achieves a viscosity of at least 500Pascal-second within 120 seconds following initiation of mixing ofmonomer and polymer components.

Optionally, the cement achieves a viscosity of at least 500Pascal-second within 60 seconds following initiation of mixing ofmonomer and polymer components.

Optionally, the cement achieves a viscosity of at least 500Pascal-second within 45 seconds following initiation of mixing ofmonomer and polymer components.

Optionally, the cement achieves a viscosity of at least 500Pascal-second within 30 seconds following initiation of mixing ofmonomer and polymer components.

Optionally, the cement achieves a viscosity of at least 500Pascal-second within 15 seconds following initiation of mixing ofmonomer and polymer components.

Optionally, a bone cement according to the invention is used in avertebroplasty and/or a kyphoplasty procedure.

Optionally, the viscosity of the cement changes by less than 10% withina subsequent 2 minutes.

Optionally, the viscosity changes by less than 20% within a subsequent 8minutes.

Optionally, the viscosity changes by less than 200 Pascal-second duringa window of at least two minutes after said mixing.

Optionally, the window begins 1 minute after said mixing.

Optionally, the window begins 2 minutes after said mixing.

Optionally, the window begins 3 minutes after said mixing.

Optionally, the window begins 6 minutes after said mixing.

Optionally, the window begins 8 minutes after said mixing.

Optionally, the portion of the polymer component of the mixture ischaracterized by a molecular weight in the range of 600,000 to 1,200,000Dalton.

Optionally, the portion comprises at least 1% of said polymer componentof the mixture.

Optionally, the portion comprises at least 2% of said polymer componentof the mixture.

Optionally, the portion comprises at least 3% of said polymer componentof the mixture.

Optionally, the portion comprises at least 5% of said polymer componentof the mixture.

Optionally, the polymer component of the mixture includes PMMA.

Optionally, the polymer component of the mixture includes styrene.

In an exemplary embodiment of the invention, there is provided a methodof treating a bone, the method comprising:

-   (a) preparing a bone cement which achieves a viscosity of at least    500 Pascal-second within 160 seconds from a time at which a polymer    component and a monomer component of the cement are contacted one    with another;-   (b) delivering the bone cement into a bone.

Optionally, the cement achieves a viscosity of at least 500Pascal-second within 90 seconds.

Optionally, the bone is a vertebra.

Optionally, the material is an acrylic polymer mixture.

In an exemplary embodiment of the invention, there is provided a systemfor delivery of a viscous material into a bone, the system comprising:

-   (a) a reservoir containing a volume of a material characterized by a    viscosity of at least 900 Pascal-second;-   (b) a pressure source adapted to apply sufficient pressure to the    material in the reservoir to expel at least 5 ml of the material    from the reservoir without retraction of a piston;-   (c) an actuator operable to activate the pressure source; and-   (d) a tube adapted to deliver said pressure from said pressure    source to said reservoir.

Optionally, the volume is at least 5 ml.

Optionally, the volume is at least 10 ml.

Optionally, the reservoir contains a piston; said piston responsive to apressure supplied by said pressure source.

Optionally, the reservoir is adapted for connection to a cannula with aninner diameter of not more than 5 mm.

Optionally, the pressure source includes a hydraulic mechanism.

Optionally, the hydraulic mechanism includes a sterile hydraulic fluid.

Optionally, the sterile hydraulic fluid is deployed in a manner whichprevents the fluid from passing through the reservoir into the body of asubject.

Optionally, the actuator is adapted to provide hydraulic amplification.

Optionally, the actuator includes a ball screw connection.

Optionally, the actuator is manually operable.

Optionally, the actuator is operable by a foot.

Optionally, the actuator is electrically operable.

Optionally, the a battery provides electric power for the electricoperation.

Optionally, the pressure source is adapted to generate a pressure of50-300 atmospheres.

Optionally, the system includes at least one pressure limitingmechanism.

Optionally, the actuator is adapted to deliver defined aliquots ofmaterial in response to separate actuations.

Optionally, the aliquots of material have a volume in the range of 0.15to 0.5 ml.

Optionally, the material is characterized by a viscosity of less than2000 Pascal-second.

In an exemplary embodiment of the invention, there is provided anapparatus for mixing, the apparatus comprising:

-   (a) a container containing at least a polymer component and a    monomer component of a bone cement to be mixed;-   (b) a mixing paddle attachable to a drive mechanism via a mixing    element axle; and-   (c) the drive mechanism adapted to move the mixing paddle along a    travel path so that a reference point on the mixing element will    face in a same direction at every point on the travel path.

Optionally, operation of the drive mechanism causes the mixing paddle topress at least a portion of the material being mixed against a wall ofthe container.

Optionally, the drive mechanism includes at least one gear.

Optionally, the mixing paddle is characterized by a surface area of atleast 600 square millimeters.

Optionally, the apparatus includes a transfer mechanism to transfer aviscous mixture out of the container of the apparatus.

In an exemplary embodiment of the invention, there is provided a bonecement with a glass transition temperature above 37 degrees Celsius.

Optionally, the cement includes polycaprolactone and/or Polylactic acid(PLA).

In an exemplary embodiment of the invention, material characterized by aglass transition temperature above 37 degrees Celsius is used informulation of a bone cement.

In an exemplary embodiment of the invention, there is provided a methodfor treating bones, the method comprising:

-   (a) providing a bone cement including a material with a glass    transition temperature above 37 degrees Celsius;-   (b) heating the material at least to its glass transition    temperature; and-   (c) injecting the material into an interior of a vertebra preventing    the material from cooling to a temperature below the glass    transition temperature.

Optionally, the method includes permitting the material to cool to 37degrees and set within the vertebra.

Optionally, the material is bioabsorbable.

Optionally, the method includes mixing the material with ground bone.

In an exemplary embodiment of the invention, there is provided a methodfor treating long bones, the method comprising:

-   (a) providing a material with a glass transition temperature above    37 degrees Celsius;-   (b) heating the material to its glass transition temperature; and-   (c) injecting the material into an interior of a medullary canal of    a long bone while maintaining the material at the glass transition    temperature.

Optionally, the inserting into a medullary canal of a long bone resultsin formation of an intra-medular nail.

In an exemplary embodiment of the invention, there is provided a bonecement delivery cannula, the cannula comprising:

-   (a) an inner lumen adapted to provide a channel of fluid    communication between a bone cement reservoir and at least one    lateral cement ejection aperture; and-   (b) a permanently axially closed distal tip.

In an exemplary embodiment of the invention, there is provided a methodof delivering bone cement to a bone, the method comprising:

-   (a) inserting a cannula characterized by an axially closed distal    tip into a bone; and-   (b) causing bone cement to flow through an inner lumen of the    cannula and exit at least one lateral aperture of the cannula.

In an exemplary embodiment of the invention, there is provided anapparatus for filling an injection reservoir with a viscous material,the apparatus comprising:

-   (a) a container capable of containing a viscous material;-   (b) a transfer piston insertable in the container so that the piston    forms a circumferential seal with respect to the container, the    transfer piston including a hole; and-   (c) a mechanism for attaching an aperture of an injection reservoir    to the hole in the transfer piston.

In an exemplary embodiment of the invention, there is provided aninjection kit, the kit comprising;

-   (a) a hydraulic pressure source capable of delivering at least 50    atmospheres of pressure to an injection reservoir;-   (b) a quantity of a fluid contained in the pressure source; and-   (c) a connector adapted for connection to an injection reservoir.

Optionally, the connector includes at least 20 cm of a flexible tubing.

Optionally, the pressure source is capable of delivering at least 100atmospheres of pressure.

Optionally, the pressure source is capable of delivering at least 200atmospheres of pressure.

Optionally, the pressure source is capable of delivering at least 300atmospheres of pressure.

In an exemplary embodiment of the invention, there is provided a methodof restoring a height of a subject, the method comprising:

-   (a) inserting a cannula into a fractured vertebra; and-   (b) injecting a sufficient quantity of a material characterized by a    viscosity of at least 500 Pascal second at the time of injection to    at least partially reduce the fracture.

Optionally, the injecting is at a pressure sufficient to overcome aresistant pressure in the vertebra.

Optionally, the pressure is at least 50 atmospheres.

Optionally, the pressure is at least 100 atmospheres.

Optionally, the pressure is at least 200 atmospheres.

Optionally, the pressure is at least 300 atmospheres.

In an exemplary embodiment of the invention, there is provided a systemfor injection of material into a bone, the system comprising:

-   (a) a reservoir containing material to be injected into a bone, said    reservoir deployed external to a body of a subject;-   (b) a pressure source adapted to apply sufficient pressure to the    material in the reservoir to expel at least a portion of the    material from the reservoir through a cannula;-   (c) an actuator operable to activate the pressure source; and-   (d) a cannula adapted for insertion into the bone, said cannula    connectable to the external reservoir;

wherein an operator of the system may perform an injection touching onlythe actuator.

Optionally, the system is used to inject material in proximity to animplant to strengthen the implant.

Optionally, a method described herein is employed as a means ofvertebroplasty.

Optionally, a system described herein is employed to perform avertebroplasty procedure.

Optionally, a cement described herein is employed in a vertebroplastyprocedure.

In an exemplary embodiment of the invention, there is provided a bonecement comprising an acrylic polymer mixture, the cement achieving aviscosity of at least 500 Pascal-second when 100% of a polymer componentis wetted by a monomer component.

Optionally, the cement achieves a viscosity of at least 500Pascal-second when 95% of a polymer component is wetted by a monomercomponent.

An aspect of some embodiments of the invention relates to both movingand supporting bone using a same material, which is not enclosed by abag to prevent migration of the material. In an exemplary embodiment ofthe invention, a material which does not set to a hardened condition isinjected into a bone which is fractured and the pressure of the injectedmaterial moves the fractured pieces of the bone. The injected materialremains in the bone to provide support and prevent retrograde motion ofthe bone, for example, permanently or until the bone heals. Optionally,an additional material or implant may be provided to further support thebone, however, the injected material supports at least 20%, optionally30%, optionally 40%, optionally 50% of the forces applied by the bonepieces, or smaller, intermediate or greater percentages. Optionally, theadditional material is a cement which sets to a hardened condition.

In an exemplary embodiment of the invention, the material used is anartificial material. In an alternative embodiment of the invention, thematerial is natural.

In various embodiments of the invention, the following types ofmaterials are used:

(a) Relatively (to bone) soft solid materials which can optionallyundergo substantial plastic deformation without tearing and optionallyinclude no cross-linking above type I. In an exemplary embodiment of theinvention, these materials are compressed radially and provided througha narrow diameter aperture into the bone. In an alternative exemplaryembodiment of the invention, the material is provided in a small profilecondition and either compressed axially for loading into a deliverysystem or simply advanced into the bone without initial compression.

In an exemplary embodiment of the invention, the soft materials areplastically deforming materials. In the example of intra-vertebral use,at least 50%, 80%, 90%, 95% or more of deformation is optionally plasticdeformation. Optionally, the materials have an elastic deformation of0.1% or less. In an exemplary embodiment of the invention, for amaterial 1 mm in thickness, elastic spring-back is less than 0.1 mm,less than 0.05 mm or less.

(b) High viscosity fluids, such as bone slurry, semi-hardened cement andputty-like materials. These materials are flowed through the deliverysystem, optionally under a high pressure. In some cases, the fluids setto a hardened condition, for example, due to a polymerization process ordue to contact with body fluids.

An aspect of some embodiments of the invention relates to fracturereduction (e.g., height restoration in a vertebra), using a softmaterial that is not constrained by an enclosure. In an exemplaryembodiment of the invention, the material is a soft material softer than60 A, 70 A, 80 A, 90 A or 100 A shore. Optionally, the material is atleast 10 A shore or 20 A shore, for example, at least 20 A or 30 Ashore.

In an alternative exemplary embodiment of the invention, the material isa flowable material, for example, with a viscosity greater than 100Pascal-second, 300 Pascal-second, 500 Pascal-second, 600 Pascal-second,800 Pascal-second, 1000 Pascal-second or more. Optionally, the materialhas a viscosity of less than 4,000 Pascal-second, optionally less than1,800 Pascal-second, optionally less than 1,400 Pascal-second,optionally less than 1,100 Pascal-second or smaller intermediate orlarger values.

An aspect of some embodiments of the invention relates to the use ofmaterials which do not set to a hardened condition for supporting bone.In an exemplary embodiment of the invention, the material is injectedinto a bone.

As used herein, the term “setting” is used to define materials whosemechanical properties, such as strength and/or hardness, increase forchemical reasons, for example, due to polymerization during and/orshortly after implantation, e.g., after a few hours, a few days or a fewweeks. It should be noted that a material which sets to a non-hardenedcondition is a setting material. A pre-set soft material will alsogenerally not set to a hardened condition.

As used herein the term “hardened condition” is used to describematerials that are 50% or more the hardness of cortical bone. In somecases it is desirable to compare the strength and/or young modulus ofthe material to cortical and/or trabecular bone, in which case, valueswithin 110% or 120% or 130% or intermediate values of the values for thebone in question bone may be desirable.

In an exemplary embodiment of the invention, the injected material isselected to have a high viscosity or is a soft material which canundergo plastic deformation, for example, by the material not tearingduring an injection via a small diameter tube. Optionally, the materialis mechanically sheared during injection.

In an exemplary embodiment of the invention, the use of a non-hardeningmaterial allows more flexibility in injection methods, due to therelieving of time constraints typically involved in using a cement whichsets to a hardened condition, such as PMMA, in which the time betweenmixing and setting and especially the time at a given viscosity range,constrains the physician. Optionally, a non-hardening material is moreconvenient to use, as it does not require the user to mix the materialat the time of use. In an exemplary embodiment of the invention, thematerial is provided in a pre-loaded magazine or delivery system.

A potential property of using a viscous or soft solid material is thatthere is less danger of leakage out of the vertebra. Optionally, variouscomponents are added to the material, for example, a bone growth factoror a radio-opaque material.

A potential advantage of some pre-set or non-setting materials is thatan exothermic setting reaction is avoided.

In an exemplary embodiment of the invention, the injected material isfree of cross-linking or includes only type I cross-linking.

Optionally, the injected material softens over time.

In an exemplary embodiment of the invention, the material is formulatedso that only hardens in the presence of water or other materials commonin the body but does not set or harden outside the body. Thus thematerial can be pre-formulated and mixed and will only set after beingintroduced into the body. Optionally, the material sets after 10-30minutes or longer.

An aspect of some embodiments of the invention relates to treatment ofbody tissues by injecting a non-solid or soft-solid material harder than10 A shore. In an exemplary embodiment of the invention, the injectedmaterial flows into or is forced into an intra-body space to be filledthereby. In an exemplary embodiment of the invention, the injectedmaterial is viscous enough or solid enough so it does not inadvertentlymigrate out of a tissue into which it is injected, for example, out of avertebra. This viscosity level used may depend on the size and/or shapeof voids leading out of the tissue being treated. Optionally, thematerial sets to a hardened condition. Alternatively, the material doesnot.

In an exemplary embodiment of the invention, the material is providedunder a pressure of greater than 40 atmospheres.

An aspect of some embodiments of the invention relates to a method ofproviding a flowable or soft-solid material into the body, in discreteunits, optionally of predetermined quantities. In an exemplaryembodiment of the invention, a delivery system with a first quantity ofmaterial is provided and a user can select a discrete amount of thisfirst quantity to be injected. This is in contrast to continuous methodsin which material is injected until a user stops the injection or thematerial is all used up. Optionally, the material to be injected isprovided in a magazine from which a unit of material can be selected forinjection. Optionally, selection is by cutting the material away fromthe magazine.

In an exemplary embodiment of the invention, a treatment for a bone isprovided by injecting two, three, four or more discrete units ofmaterial.

A potential advantage of working in discrete portions which areconsiderably smaller than a total therapeutic amount, in someembodiments of the invention, is that a friction between the materialand a delivery system is reduced, as the amount of material advanced ateach time is reduced.

An aspect of some embodiments of the invention relates to using a sleevefor delivering material or a device implant that have a high friction toa delivery system, to a site inside the body. In an exemplary embodimentof the invention, the sleeve is designed to reduce friction between thedelivered material and a delivery system. Optionally, the sleeve isprovided inside of a delivery tube. Optionally, force is applieddirectly on the sleeve to deliver the material or implant.

An aspect of some embodiments of the invention relates to a system fordelivering material into a bone which system is adapted to travel over aguidewire. Optionally, the system travels over a guidewire when loaded.Alternatively or additionally, the system is loaded after beingintroduced into the body. In an exemplary embodiment of the invention,the system comprises a distal end adapted to penetrate bone, for examplevertebral bone. In an exemplary embodiment of the invention, the systemis adapted to deliver the material into a vertebra in a manner whichwill at least partially restore a height of said vertebra. In anexemplary embodiment of the invention, the material surrounds theguidewire.

An aspect of some embodiments of the invention relates to a system fordelivering material into a bone under pressure, the system being adaptedto penetrate bone. In an exemplary embodiment of the invention, thesystem comprises a distal tip adapted to penetrate bone. Optionally, anaperture is formed near the distal tip for delivering of said material.

An aspect of some embodiments of the invention relates to materials foruse in the body for supporting hard tissue and which do not set to ahardened condition when in storage (e.g., for over 1 hour or over oneday or 1 week). In an exemplary embodiment of the invention, thematerial comprises polymers without cross-linking or with type Icross-linking. Optionally, the composition of the material is a mixtureof Laurylmethacrylate (LMA) and methylmethacrylate (MMA), for example ina ratio of between 90:10 and 10:90. Optionally, the material isthermoplastic rather than thermosetting.

In an exemplary embodiment of the invention, the material is aputty-like material. In one example, the material is composed of amixture of hydroxyapatite and sufficient sodium alginate, such that themixture remains putty like after time, at least if not in contact withwater.

In an exemplary embodiment of the invention, the material softens overtime. Optionally, the material is composed of MMA and LMA with poly-hemaadded, and softens by the absorption of body fluids by the composition.

Alternatively or additionally, water soluble materials, such as salts ormaterials which degrade in body fluids, such as some sugars andplastics, are added and when they degrade, soften the material.

In an exemplary embodiment of the invention, the material hardens overtime, but does not harden completely. Optionally, the material includesa solvent, such as NMP (N-methyl pyrolidone), which is soluble in waterand as it is carried away, the material hardens somewhat.

Optionally, the actually injected material includes one or more addedcomponents. Optionally, one or more of a radio opaque marker,antibiotic, anti-inflammatory and/or bone growth factor, are provided asthe added components. Optionally, an added component is added by volumeof less than 30% of the material volume and in total less than 50% forall the added components.

Optionally, the added materials are chemically inert but may have astructural effect, for example, due to bulk thereof.

Optionally, non-inert materials are added, for example, 5% of a cementwhich sets to a hardened condition may be added. Optionally, suchnon-inert materials are mixed-in at a coarse grain.

An aspect of some embodiments of the invention relates to using amaterial which sets to a hardened condition, which maintains a highviscosity value during a substantial window of time. In an exemplaryembodiment of the invention, the viscosity is between 600 Pascal-secondand 1,800 Pascal-second during a period of at least 5 or at least 8minutes or greater or intermediate values. In an exemplary embodiment ofthe invention, the material is composed of a mixture of PMMA beadsand/or styrene beads and MMA monomers, with the increase in viscositybeing provided by the size of the beads of, for example, 10-200 micronsand/or by changing the ratio between beads and liquid MMA monomer,and/or by changing molecular weight of polymer in the beads. Optionally,as setting progresses, viscosity due to the beads is replaced/increasedby viscosity due to the polymerization process. Alternatively oradditionally, addition of Butyl Methacrylate to PMMA provides anincrease in viscosity for any given ratio between monomer and polymerand/or for any given set of bead parameters.

An aspect of some embodiments of the invention relates to treatingcompression fractures by heating a compressed vertebra. Optionally, theheating is provided by a stand-alone tool. Optionally, the heating isprovided to replace heating which is otherwise provided by the settingof a cement. Optionally, a thermocouple or other temperature sensor isused to control the amount of heating provided.

An aspect of some embodiments of the invention relates to a method ofselecting mechanical properties of an implant to match those of a bone,cortical and/or trabecular, being treated. In an exemplary embodiment ofthe invention, one or more of hardness, strength and/or Young modulusare matched.

There is thus provided in accordance with an exemplary embodiment of theinvention, a method of treating a vertebra, comprising:

(a) accessing an interior of a vertebra; and

(b) introducing a sufficient amount of artificial biocompatible materialwhich does not set to a hardened condition in storage, into said bone,with sufficient force to move apart fractured portions of said bone.

Optionally, said material does not set to a hardened condition afterintroduction into the body.

In an exemplary embodiment of the invention, said material can be storedfor over 1 day.

In an exemplary embodiment of the invention, said material softens afterimplantation.

In an exemplary embodiment of the invention, said material partlyhardens after implantation.

In an exemplary embodiment of the invention, said material does set to ahardened condition after introduction into the body.

In an exemplary embodiment of the invention, said material does not setto a hardened condition in storage.

In an exemplary embodiment of the invention, said material isartificial.

In an exemplary embodiment of the invention, said material is aplastically deforming material. Optionally, said material has a hardnessof between 10 A shore and 100 A shore and/or a Young modulus higher than200 MPa. Alternatively or additionally, said material is free ofcross-linking higher than type I. Alternatively or additionally, saidmaterial is thermoplastic. Alternatively or additionally, said materialcomprises LMA (lauryl methacrylate) and MMA (methyl methacrylate).

In an exemplary embodiment of the invention, said material is a viscousfluid. Optionally, said material has a viscosity between 600Pascal-second and 1,800 Pascal-second.

In an exemplary embodiment of the invention, introducing comprisesintroducing at a pressure of at least 40 atmospheres.

In an exemplary embodiment of the invention, introducing comprisesintroducing at a pressure of at least 100 atmospheres.

In an exemplary embodiment of the invention, introducing comprisesintroducing through a delivery channel having a diameter of less than 6mm and a length of at least 70 mm.

In an exemplary embodiment of the invention, introducing comprisesintroducing through an extrusion aperture having a minimum dimension ofless than 3 mm.

In an exemplary embodiment of the invention, introducing comprisesintroducing through an extrusion aperture having a minimum dimension ofless than 1.5 mm.

In an exemplary embodiment of the invention, introducing comprisesintroducing through a plurality of extrusion apertures simultaneously.

In an exemplary embodiment of the invention, introducing compriseschanging an introduction direction during said introduction.

In an exemplary embodiment of the invention, introducing compriseschanging an introduction position during said introduction.

In an exemplary embodiment of the invention, said material comprises atleast one material adapted to function in a capacity other thanstructural support.

In an exemplary embodiment of the invention, introducing comprisesadvancing said material using a motor.

In an exemplary embodiment of the invention, introducing comprisesadvancing said material using a hydraulic source.

In an exemplary embodiment of the invention, introducing comprisesintroducing said material in discrete unit amounts. Optionally, at leastsome of the units have different mechanical properties form each other.

In an exemplary embodiment of the invention, introducing comprisescutting said material away from a delivery system.

In an exemplary embodiment of the invention, introducing comprises nottwisting said material during said introducing.

In an exemplary embodiment of the invention, introducing comprisesshaping an extrusion form of said material using an exit aperture.

In an exemplary embodiment of the invention, accessing comprisesaccessing using a guidewire and providing a delivery system over theguidewire.

In an exemplary embodiment of the invention, accessing comprisesaccessing using a delivery system of said material.

In an exemplary embodiment of the invention, introducing comprisesintroducing without a separate void forming act.

In an exemplary embodiment of the invention, introducing comprisesintroducing without a spatially constraining enclosure.

In an exemplary embodiment of the invention, introducing comprisesintroducing in a spatially constraining enclosure.

In an exemplary embodiment of the invention, introducing comprises alsointroducing at least 10% by volume of a material which sets to ahardened condition.

In an exemplary embodiment of the invention, the method comprisesselecting said material to have at least one of hardness and Youngmodulus properties less than those of trabecular bone of said vertebra,after a week from said implantation.

In an exemplary embodiment of the invention, said introduced material isoperative to support at least 30% of a weight of vertebra within a weekafter implantation.

There is also provided in accordance with an exemplary embodiment of theinvention, a surgical set comprising:

at least one tool adapted to deliver a material into a vertebra; and

at least 1 cc of artificial biocompatible prepared material that doesnot set to a hardened condition outside the body. Optionally, said atleast one tool comprises a pressure delivery mechanism capable ofdelivering said material at a pressure of above 100 atmospheres.Alternatively or additionally, said set comprises a disposable hydraulicactuator. Alternatively or additionally, said set comprises areplaceable magazine for storing said material.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of treating bone, comprising:

(a) accessing an interior of a bone; and

(b) introducing a sufficient amount of biocompatible material into saidbone, without an enclosure between said material and the bone, saidintroducing being with sufficient force to move apart fractured portionsof said bone. Optionally, the method comprises leaving said material insaid bone to resist at least 30% of a normative force which urges saidportions together.

Optionally, said bone is a vertebra. Optionally, said material does notset to a hardened condition in storage. Alternatively or additionally,said material does not set to a hardened condition in the body.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of treating a vertebra, comprising:

(a) accessing an interior of a vertebra; and

(b) introducing a sufficient amount of spatially unconstrainedbiocompatible soft material having a hardness of less than 100 A Shoreinto said vertebra, with sufficient force to move apart fracturedportions of said bone.

There is also provided in accordance with an exemplary embodiment of theinvention, a surgical set comprising:

at least one tool adapted to deliver a material into a vertebra; and

at least 1 cc of biocompatible prepared material that has a Youngmodulus of less than 120% of healthy vertebral trabecular bone and isprepared at least 1 day ahead of time.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of treating a bone, comprising:

(a) accessing an interior of a bone; and

(b) introducing, via a delivery tube, into said bone an unconstrainedplastically deformable solid material harder than 10 A shore and softerthan 100 A shore.

There is also provided in accordance with an exemplary embodiment of theinvention, apparatus for delivering a material or an implant into abone, comprising:

(a) a delivery tube having a lumen and a distal end adapted forinsertion into a body;

(b) a payload comprising at least one of material and an implant insidesaid lumen;

(c) a lining disposed between said tube and said payload; and

(d) an advancing mechanism adapted to move said liner and said payloadto said distal end,

wherein said liner reduces a friction of said payload against saiddelivery tube. Optionally, the apparatus comprises a splitter whichsplits said sleeve.

In an exemplary embodiment of the invention, said mechanism pulls saidsleeve.

In an exemplary embodiment of the invention, said mechanism pushes saidpayload.

In an exemplary embodiment of the invention, said sleeve folds over saiddelivery tube.

There is also provided in accordance with an exemplary embodiment of theinvention, a biocompatible material which does not set to a hardenedcondition and does not include cross-linking of a type greater than typeI and formed of MMA (methyl methacrylate). Optionally, said material isformed of a mixture of MMA and LMA (lauryl methacrylate)

There is also provided in accordance with an exemplary embodiment of theinvention, a second medical use of PMMA for height restoration ofvertebral bones when applied directly into a vertebra. Optionally, saidPMMA is applied during setting while at a viscosity higher than 400Pascal-second.

There is also provided in accordance with an exemplary embodiment of theinvention, a second medical use of bone putty for vertebral treatmentwhen applied under pressure through a tubular delivery system into avertebral bone.

There is also provided in accordance with an exemplary embodiment of theinvention, a polymerizing composition, comprising:

(a) a first quantity of beads having a set of sizes; and

(b) a second quantity of monomer,

wherein said quantities are selected so that a mixture of saidquantities results in a setting material having a workability window ofat least 5 minutes at a viscosity between 500 and 2000 Pascal-second.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of treating bone, comprising providing a heat sourceinto a vertebra in a controlled manner.

There is also provided in accordance with an exemplary embodiment of theinvention, a composite tool for accessing bone, comprising:

an elongate body having:

-   -   (a) a head adapted to penetrate bone;    -   (b) an aperture adapted to extrude material into bone, near said        head; and    -   (c) a lumen adapted to deliver material to said aperture; and

a source of material under pressure. Optionally, the tool comprises alumen for a guidewire.

There is also provided in accordance with an exemplary embodiment of theinvention, a composite tool for accessing bone comprising:

a drill tool including a lumen;

a separable guidewire adapted to fit in said lumen; and

a handle adapted to control the relative positions of said drill tooland said guidewire.

There is also provided in accordance with an exemplary embodiment of theinvention, bone cement comprising:

a polymer component; and

a monomer component,

wherein, when the two components are mixed together, the resultingmixture attains, within a period of up to 2 minutes, a putty-likeconsistency

wherein the viscosity of the resulting mixture remains approximatelyconstant during a period of time of at least 5 minutes.

BRIEF DESCRIPTION OF THE FIGURES

Exemplary non-limiting embodiments of the invention will be describedwith reference to the following description of embodiments inconjunction with the figures. Identical structures, elements or partswhich appear in more than one figure are generally labeled with a sameor similar number in all the figures in which they appear, in which:

FIG. 1A is a general flowchart of a process of treating a compressionfracture, in accordance with an exemplary embodiment of the invention;

FIG. 1B is a more detailed flowchart of a process of treating acompression fracture, in accordance with an exemplary embodiment of theinvention;

FIG. 2 shows a composite tool for accessing a vertebra, in accordancewith an exemplary embodiment of the invention;

FIGS. 3A-3F show stages of a method of treatment according to FIGS. 1Aand 1B, in an exemplary implementation of the method;

FIGS. 4A and 4B illustrate basic material delivery systems, inaccordance with exemplary embodiments of the invention;

FIGS. 5A and 5B show details of material extruder tips, in accordancewith exemplary embodiments of the invention;

FIG. 5C shows an elongated and curved extrusion of material, inaccordance with an exemplary embodiment of the invention;

FIGS. 6A-6C illustrate narrowing lumen sections of a delivery system, inaccordance with an exemplary embodiment of the invention;

FIG. 7A illustrates a hydraulic delivery system, in accordance with anexemplary embodiment of the invention;

FIGS. 7B and 7C show alternative methods of providing hydraulic power tothe system of FIG. 7A, in accordance with exemplary embodiments of theinvention;

FIGS. 7D and 7E illustrate an exemplary hydraulic system including adisposable unit, in accordance with an exemplary embodiment of theinvention;

FIGS. 7F-7G illustrate an exemplary hydraulic delivery system, inaccordance with an exemplary embodiment of the invention;

FIG. 7H illustrates an exemplary hydraulic delivery system, inaccordance with an exemplary embodiment of the invention;

FIG. 7I is a cross sectional view of a hydraulic actuator for a deliverysystem in accordance with an exemplary embodiment of the invention; theinset shows a portion of the actuator in greater detail;

FIGS. 7J and 7K are exploded and cross sectional views respectively of aportion of a hydraulic actuator for a delivery system in accordance withan exemplary embodiment of the invention;

FIG. 7L is an exploded view of a pressure release valve for a deliverysystem in accordance with an exemplary embodiment of the invention;

FIGS. 7M, 7N and 7O are cross sectional views and a side view of apressure release valve for a delivery system in operation in accordancewith an exemplary embodiment of the invention;

FIGS. 7P and 7Q are cross sectional views of a cement reservoirillustrating a floating piston according to some exemplary embodimentsof the invention;

FIGS. 7R and 7S are cross sectional views of a cement reservoirillustrating assembly of a distal injection port according to someexemplary embodiments of the invention;

FIG. 7T is a cross sectional view of a cement reservoir according to anadditional exemplary embodiment of the invention;

FIG. 7U is a perspective view of a foot operated actuator suitable foruse in a delivery system according to some embodiments of the invention;

FIG. 7V is a cut away view of a foot operated actuator suitable for usein a delivery system according to some embodiments of the invention;

FIGS. 7W, 7X, 7Y, and 7Z are additional views of a foot operatedactuator suitable for use in a delivery system according to someembodiments of the invention;

FIG. 8A shows a cassette based delivery system, in accordance with anexemplary embodiment of the invention;

FIG. 8B is a detail showing the delivery of unit element, in accordancewith an exemplary embodiment of the invention;

FIGS. 9A and 9B show a material pusher with reduced material twisting,in accordance with an exemplary embodiment of the invention;

FIG. 10A-10F show sleeve based material pushers, in accordance withexemplary embodiments of the invention;

FIGS. 11A and 11B show squeeze based delivery systems, in accordancewith exemplary embodiments of the invention;

FIGS. 12A and 12B illustrate a one step access and delivery system, inaccordance with an exemplary embodiment of the invention;

FIG. 12C shows an over-the-wire delivery system, in accordance with anexemplary embodiment of the invention; and

FIG. 13 is a graph showing compressibility of a material in accordancewith an exemplary embodiment of the invention;

FIGS. 14A and 14B are exploded and perspective views respectively of anexemplary apparatus for mixing viscous material, in accordance with someembodiments of the invention;

FIGS. 14C1, 14C2, 14C3 and 14C4 are a series of top views illustratingan exemplary travel path of a mixing element within a mixing well of theexemplary apparatus of FIGS. 14A and 14B;

FIG. 15 is a graph of viscosity (Pascal Sec) as a function of time(minutes) for an exemplary cement according to the invention and anexemplary prior art cement;

FIGS. 16 and 17 are graphs indicating viscosity as Newtons of appliedforce per unit displacement (mm) under defined conditions for exemplarycements according to the invention and illustrate the time window forinjection which is both early and long;

FIGS. 18, 19, 20 and 21 are perspective views of an exemplary embodimentof a transfer apparatus for loading a viscous material into a container;and

FIGS. 22; 23; 24; 25 and 26 illustrate an additional exemplaryembodiment of a transfer apparatus.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Overview of Exemplary Process

FIG. 1A is a general flowchart 100 of a process of treating acompression fracture, in accordance with an exemplary embodiment of theinvention.

At 102, a bone to be treated is identified. In the case of a vertebra,this usually involves X-ray or CT images to identify a vertebra or otherbone that is fractured, for example by a compression fracture. Thefollowing description focuses on vertebral compression fractures butsome embodiments of the invention are not limited to such cases.

In an exemplary embodiment of the invention, the access is minimallyinvasive, for example, only a single channel is formed into the body.Optionally, the procedure is carried out via a cannula having a diameterof, for example of 5 mm, 4 mm or less in diameter is inserted into thebody. In some cases, multiple openings into the body are formed. Theprocedure can also be carried out using a surgical or key-hole incision;however, this may require a longer recuperation period by the patient.Optionally, the cannula (and corresponding length of a delivery tubedescribed below) is at least 50 mm, 70 mm, 100 mm or more orintermediate or smaller values.

At 104, the vertebra is accessed.

At 106, a material, having a high viscosity in some embodiments of theinvention, is injected into the vertebra. Optionally, the vertebra isfractured due to weakening caused by osteoporosis or other pathologicalconditions.

At 108, material is optionally provided in a manner and/or amount whichrestores at least part of the height of the vertebra, for example, 20%,40%, 50% or intermediate or a higher percentage of a pre-compressionheight. A particular feature of some embodiments of the invention isthat the provided material is of sufficient viscosity or sufficientlysolid that leakage from the vertebra is reduced or prevented, ascompared to liquid PMMA cement. A pressure used to advance the materialmay be higher than what is known in the art to match the increasedviscosity.

At 110, the procedure is completed and the tube is removed.

Exemplary Bone Access Set

Before going into the details of the procedure, the tools used are firstdescribed. FIG. 2 shows a composite tool 200 optionally used foraccessing the bone, in accordance with an exemplary embodiment of theinvention. In an exemplary embodiment of the invention, the access toolsused comprise a set of component tools that interlock to act,selectively, as a single tool or as separate tools. In an exemplaryembodiment of the invention, this composite set/tool serves as a onestep access system in which only a single insertion of objects into thebody is required. Optionally, as described below, the delivery system isalso inserted at the same time. Optionally, a cannula portion of thetool is omitted, for example as described in the embodiments of FIGS.12A-12C.

In an exemplary embodiment of the invention, the components of tool 200are coaxially matched components, which fit one within the lumen of thenext.

An optional cannula 202 comprises a handle 204 and a body including alumen.

An optional drill tool 206 includes an elongate body adapted fordrilling and a handle 208. Optionally, handle 208 selectivelyrotationally locks to handle 204, for manipulation using a single hand,optionally using a snap-lock 217. The body of tool 206 fits in the lumenof cannula 202. Optionally, a section 210 of tool 206 is marked to bevisible on an x-ray image, even in contrast to cannula 202. Optionally,this allows the difference in diameters between cannula 202 and drilltool 206 to be minimal. Absent such a marker, in some cases, thedifference in diameters may not be visible on an x-ray image and the twotools cannot be distinguished.

An optional guidewire 212 is provided inside a lumen of drill tool 206.Optionally, a knob or other control 214 is provided for selectiveadvancing and/or retracting of guidewire 212 relative to drill 216. Theknob may be marked with relative or absolute positions.

Optional depth marking are provided on cannula 202.

An exemplary use of these tools will be described below, in which FIGS.3A-3F schematically show the progress as a vertebra 300 having acompression fracture 306 is being treated, paralleling a detailedflowchart 120 shown in FIG. 1B.

Penetrate to Bone

At 122 (FIG. 1B), a passage is formed to the bone through a skin layer312 and intervening tissue, such as muscle and fat. Optionally, thepassage is formed by advancing composite tool/set 200 until a tip 218 ofguidewire 212 contacts the bone. In some embodiments, tip 218 isdesigned to drill in soft tissue (e.g., includes a cutting edge).Alternatively or additionally, tip 218 includes a puncturing pointadapted to form a puncture in soft tissue.

This is shown in FIG. 3A. Also shown are cortical plates 302 and 304 ofthe vertebra and a cancellous bone interior 308.

A single pedicle 310 is shown, due to the view being cross-sectional.Optionally, the access to the vertebra is via a pedicle. Optionally, theaccess is via both pedicles. Optionally, an extrapedicular approach isused. Optionally, the access point or points are selected to assist inan even lifting of the vertebra.

Penetrate Bone

At 124, tip 218 penetrates through the cortex of the bone being treated(FIG. 3B). In an exemplary embodiment of the invention, tip 218 isseparately manipulated from the rest of composite tool 200. Optionally,tip 218 is advanced until it contacts a far side of the vertebra.

In an exemplary embodiment of the invention, tip 218 of guidewire 212 isformed to drill in bone and is advanced through the vertebral cortex byrotation or vibration. Optionally, it is advanced by tapping thereon orapplying pressure thereto.

Optionally, a relative position of the guidewire and the cannula isnoted, to assist in determining the inner extent of the vertebra.

At 126, the guidewire is optionally retracted. Optionally, the guidewireis axially locked to drill tool 206. Optionally, guidewire 212 and drilltool 206 align so that tip 218 and a tip 216 of the drill tool form asingle drilling tip.

At 128, drill tool 206 is advanced into the bone (FIG. 3C). Optionally,tip 216 of drill tool 206 designed for drilling and/or is advanced, forexample, by tapping, rotation and/or vibration. Optionally, the drilltool is advanced to the far side of the vertebra. Optionally, theprevious depth marking of the guidewire is used to limit this advance.Optionally, the guidewire is not retracted at 126. Instead, drill tool206 is advanced over the guidewire until it reaches the end of theguidewire.

At 130, cannula 202 is optionally advanced to the bone over the drill.Optionally, the leading edge of the cannula is threaded or otherwiseadapted to engage the bone at or about the bore formed by the drilltool. Optionally, the cannula is inserted into the bone.

At 132, the guidewire and/or drill tool are optionally removed (FIG.3D).

In some embodiments, the cannula is not advanced all the way to thebone. In others, the cannula may be advanced into the bone, for example,to prevent contact between the treatment and cortical bone and/or weakor fractured bone. Optionally, the cannula is advanced past the pedicleand to the vertebral interior 308.

Optionally, a reamer (not shown) is inserted into the cannula and usedto remove tissue from interior 308.

Inject Material

At 134, a material delivery system 314 is provided into cannula 202(shown in FIG. 3E). Optionally, the delivery system delivers material toa side thereof (described below).

At 136, system 134 is activated to inject material 316 into interior308. FIG. 3E shows that when enough material is injected, vertebralheight may be partially or completely restored. The injected materialmay partially or completely compress interior 308.

Feedback

At 138, feedback is optionally provided to an operator, to decide ifinjection is completed. Optionally, feedback is provided by fluoroscopicimaging of the site. However, other imaging methods may be used.

Optionally, non-imaging feedback is provided, for example a pressureinside the vertebra, using a pressure sensor (not shown), or using anindicator (visual or audio) for the amount of material injected.

Optionally, the feedback is used to decide if the procedure isprogressing as desired, e.g., desired amount of height restoration (ifany), verify a lack of material leakage, determine symmetry or asymmetryand/or the presence of new fractures in bone.

Repeat and/or Change

Optionally, the material is provided in a magazine having a fixed amount(described below). If that magazine is finished and additional materialis required, a refill may be provided (140), for example by replacingthe magazine with a new one.

Optionally, a property of the delivery of material is changed, forexample one or more of a delivery pressure, a delivery rate, an amountof delivery when delivery is in discrete units, a viscosity, compositionand/or type of the delivered material, a pre-heating or pre-cooling ofthe material, a location of provision inside the vertebra, a spatialpattern of provision and/or a direction of provision in the vertebra.

Optionally, the direction of provision of the material is changed (142),for example, to assist in maintaining symmetry of lifting or to point inthe injection of material away from a fracture or towards an emptyspace. Optionally, the direction of provision is changed by rotatingdelivery system 314. Alternatively or additionally, injection iscontinued through a new access hole in the vertebra. Optionally, thecannula is moved axially.

Optionally, a different material is used to top off the procedure, forexample, a cement which sets to a hardened condition (e.g., PMMA) isused to seal the entry hole and/or stiffen the non-hardening material(144).

Complete Procedure

At 146, the tools are removed. FIG. 3F shows vertebra 300 after theprocedure is completed. Optionally, the entry incision is sealed, forexample, using tissue glue or a suture.

Exemplary Basic Delivery System

FIGS. 4A and 4B illustrate basic delivery systems, in accordance withexemplary embodiments of the invention

FIG. 4A is a cross-sectional view of a delivery system 400, comprisinggenerally of a delivery tube 402 having one or more extrusion apertures404. Optionally, the distal end of tube 402 is sealed. Alternatively itmay be at least partially open, so forward injection of material isprovided. It is noted that when the end is sealed, there may be lessforce acting to retract the delivery system from the vertebra. Materialinside tube 402 is advanced by a threaded pusher 406.

In the design shown, tube 402 is attached to a barrel 408 with apermanent or temporary attachment method. Threading (not shown) may beprovided inside of barrel 408, to match the threading on pusher 406.Alternatively (not shown), the inner diameter of barrel 408 is greaterthan that of tube 402. Optionally, barrel 408 and/or tube 402 serve as areservoir of material.

A body 410 which acts as a nut and includes an inner threading engagespusher 406. In an exemplary embodiment of the invention, when a handle412 of pusher 402 is rotated (while holding on to body/nut 410), pusher406 is advanced, injecting material out of apertures 404 into the body.Optionally, barrel 408 is detachable from body 410, for example, forreplacing barrel 408 with a material-filled barrel, when one barrel isemptied. The coupling can be, for example, a threading or a quickconnect, for example, a rotate-snap fit. Optionally, tube 402 isdetachable from barrel 408, for example using the same type of coupling.

In an exemplary embodiment of the invention, when the distal tip ofpusher 406 goes past apertures 404 (in embodiments where it is thatlong), the passage cuts the material in front of the pusher away fromthe material exiting the aperture, releasing the exiting material fromthe delivery system.

FIG. 4B shows an alternative embodiment of a delivery system, 420, inwhich a different design of apertures 424 is used. In the embodiment, adelivery tube 422 serves as a barrel and storage for the material and isoptionally detachable from a threaded nut body 430. Optionally, tube 422is long enough to include an amount of material sufficient forinjection, for example, 8-10 cc. Optionally; body 430 includes a pistolor other grip (not shown) and, as above, may be threaded to engage apusher 426.

In an exemplary embodiment of the invention, the delivery system is madeof metal, for example, stainless steel. Alternatively or additionally,at least some of the components are made of a polymer material, forexample, PEEK, PTFE, Nylon and/or polypropylene. Optionally, one or morecomponents are formed of coated metal, for example, a coating withTeflon to reduce friction.

In an exemplary embodiment of the invention, the threading of the pusheris made of Nitronic 60 (Aramco) or Gall-Tough (Carpenter) stainlesssteels.

In an exemplary embodiment of the invention, instead of a standardthreading, a ball screw is used. Optionally, the use of a ball screwincreases energy efficiency and makes operation easier for manualsystems as shown in FIGS. 4A and 4B. Optionally, a gasket is provided toseparate the balls from the material.

In an exemplary embodiment of the invention, the delivered material isprovided as an elongate sausage with a diameter similar to that of thedelivery tube and/or aperture(s). Optionally, a long delivery tube isprovided. Alternatively, a plurality of such strings/sausages areimplanted. Optionally, the material is provided in a diameter smallerthan that of the delivery tube, for example, 0.1-0.01 mm smaller so thatthere is reduced friction.

Exemplary Extrusion Details

Referring back to FIG. 4A, it is noted that the more proximal extrusionaperture 404 is optionally smaller than the more distal one. Optionally,the relative sizes are selected so that the extrusion rate and/or forcesat the two holes is the same. Alternatively, the holes are designed sothat the rates and/or forces are different. Referring to FIG. 4B, threeaxially spaced apertures may be provided and the profile of extrusioncan be that a greatest extrusion and/or force is applied at the middlehole.

In an exemplary embodiment of the invention, the sizes of apertures areselected so that the total amount of material ejected is as desired,taking into account the possible sealing of some of the apertures by theadvance of the pusher.

In an exemplary embodiment of the invention, the apertures are designedso that the extruded material is ejected perpendicular to the deliverysystem. Optionally, the delivery system is shaped so that the ejectionis at an angle, for example, an angle in the plane of the axis and/or anangle in a plane perpendicular to the axis. Optionally, the angle isselected to offset forces which tend to push the delivery system out ofthe vertebra. Alternatively or additionally, the angle is selected tomatch a desired lifting direction of the vertebra or, for example, toprevent direct lifting by the extruded material. Optionally, thedelivery system is inserted at a desired angle into the vertebra.Optionally, the angles of different apertures, for example, apertures onopposite sides of the delivery tube, are different, for example,defining a 180 degree angle between the apertures on opposite sides or amore acute (towards the proximal side) or oblique angle. In an exemplaryembodiment of the invention, the extrusion angle is 30 degrees, 45degrees, 60 degrees, 80 degrees or smaller, intermediate or largerangles to the tube axis. Optionally, the material is extruded with abend radius of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 10 mm or intermediate,smaller or larger radii.

The radial arrangement of the extrusion apertures can be of variousdesigns. In one example, for example to ensure even filling of space308, three, four or more axial rows of apertures are provided. Each rowcan have, for example, one, two, three or more apertures. In anotherexample, apertures are provided only on opposing sides, so that, forexample, a user can select if to extrude towards cortical plates 302and/or 304, or not.

Rather than rows, a staggered arrangement may be used. One possibleadvantage for a staggered arrangement is that the delivery tube may beoverly weakened by aligned rows of apertures.

FIG. 5A shows a design of a delivery tip 500 in which round apertures502 in a staggered row design are used. FIG. 5B shows a design of adelivery tip 510 in which elongated rectangular apertures 512 arearranged in a non-staggered manner.

As shown, the shape of the apertures can be various, for example, round,ellipsoid, rectangular, axially symmetric or asymmetric, parallel to thetube axis or not and/or elongate. Optionally, the edges of the aperturesare jagged. Optionally, the shape of the apertures is selected for oneor more of the following reasons: shape of extrusion, preventing failureof the aperture and/or preventing failure of the delivery tip.Optionally, the apertures have a lip (optionally pointing inwards),which may assist in shaping the extrusion. For example, the lip may bebetween 0.1 and 1 mm in width, for example, 0.3 mm or 0.5 mm.

In an exemplary embodiment of the invention, the delivery tube is rigid.Optionally, the delivery tube is flexible or is mechanically shaped(e.g., using a vise) before insertion. In an exemplary embodiment of theinvention, the cannula is flexible and allows the insertion of adelivery tube which is curved at its end.

In an exemplary embodiment of the invention, the type of delivery tipused is selected by a user. Optionally, the delivery tip is replaceable,for example attached by a threading to the delivery system.

Optionally, an overtube or ring is selectively provided over part of thedelivery system to selectively block one or more of the apertures.

Referring briefly to FIG. 7A, a closed distal tip 702 of cannula 710 isshown, in which a guiding incline 706 is provided to guide the ejectedmaterial out of a lateral aperture 704. Optionally, the use of such anincline reduces turbulence in the flow/distortion of the material and/ormay assist in reducing friction and/or improving control over the shapeof the extrusion. Also to be noted is that material extrusion isprovided on only one side of the delivery system. This may allow bettercontrol over the force vectors inside the vertebra, caused by theextrusion. In an exemplary embodiment of the invention, the anglesdefined by the guiding incline (90 degrees and in the plane of the tubeaxis) help determine the extrusion direction.

Also shown in FIG. 7A is a non-twisting pusher 708, which may reduceturbulence, friction and/or other difficulties in extruding thematerial, such as voids.

FIG. 5C shows a cannula delivery tip 520, from which a material 526 isextruded by a pusher 528 in a curved extrusion shape 522. In anexemplary embodiment of the invention, the curvature is controlled bycontrolling the relative friction on a proximal side 532 and on a distalside 530 of a lateral aperture 524. Alternatively or additionally, thedegree of curvature depends on the size of the aperture and the shape ofthe incline. Optionally, the material is plastically deformed by theextrusion and may maintain a shape conferred thereby barring contactwith a deforming surface (e.g., a bone plate). In an exemplaryembodiment of the invention, a distal tip of the cannula is closed,optionally permanently closed, so that cement 522 is forced laterallyoutwards via aperture 524.

Alternatively or additionally, extrusion 522 can be curved or bent dueto axial or rotational motion of tip 520. Optionally, the rotation isused to more uniformly fill space 308.

In an exemplary embodiment of the invention, the delivery tube movesand/or rotates during delivery. Optionally, a gear mechanism couplesmovement of the pusher with rotation and/or axial motion of the tube.Optionally, a manual motion is provided by an operator. Optionally, avibrator is coupled to the delivery system.

One consideration mentioned above, is that the amount of material inbarrel 408 may not be sufficient for a complete procedure. A matchingdesign is illustrated in FIG. 6A, in which the diameter of an innerlumen 602 of barrel 408 is the same as the diameter of an inner lumen604 of delivery tube 402. A longer delivery tube/barrel maybe requiredto reduce the number of barrel changes.

FIG. 6B shows an alternative design, in which a barrel 408′ has a lumen606 with a greater inner diameter and thus a greater storage volume.Optionally, the greater diameter provides an additional hydraulicamplification factor as the diameter changes. Optionally, a suddenchange in diameter may cause turbulence, resistance and/or voidcreation. In some materials, diameter change requires compression of thematerial. Optionally, as shown, a gradual change in diameter isprovided, with an intermediate sloped section 608 with an inner diametervarying between the diameters of lumen 606 and 604. Optionally, thepusher has a diameter matching lumen 606 and does not fit into lumen604. Optionally, an extension is provided to the pusher, which extensiondoes fit in lumen 604.

Referring to FIG. 6C, a gradually changing lumen 610 is provided in abarrel 408″. Optionally, the distal end of the pusher is made of aflexible material, which can conform to the change in diameter.Optionally, the flexible material is harder than the injected material.Alternatively or additionally, the distal end of the pusher is shaped tomatch the geometry of lumen 610.

In an exemplary embodiment of the invention, the lumen of the barrel islarger than the diameter of the pusher, at least in a proximal sectionof the barrel. After the pusher advances an amount of material into thebone, the pusher is retracted and the material remaining in the barrelis rearranged so that the next advance of the pusher will advance it.Optionally, the rearranging is by advancing a second plunger having adiameter similar to that of the barrel. Optionally, this plunger iscoaxial with the pusher.

The delivery tube may have various cross-sectional shapes, for example,circular, rectangular, arcuate and/or square. Optionally, thecross-section is matched to the shape of extrusion apertures.Optionally, the inside of the apertures is made sharp to cut theextruded material as it is advanced, instead of or in addition toplastically deforming or shearing it.

Exemplary Viscosity/Plasticity and Pressure

In an exemplary embodiment of the invention, the viscosity of the bonecement is 500, optionally 1,000, optionally 1,500, optionally 2,000Pascal-sec or lesser or greater or intermediate values at the time ofloading to an injection system, optionally 3, or 2 or 1 minutes orlesser or intermediate values after mixing. Optionally, a cement withviscosity in this range is useful in vertebral repair, for example invertebroplasty and/or kyphoplasty procedures. In an exemplary embodimentof the invention, use of a cement which is viscous at the time ofinjection reduces the risk of material leakage. Reduced leakageoptionally contributes to increased likelihood of a positive clinicaloutcome.

In an exemplary embodiment of the invention, cement is sufficientlyviscous to move the bone as it is injected. Optionally, moving of thebone contributes to fracture reduction and/or restoration of vertebralheight.

In an exemplary embodiment of the invention, the provided material has aviscosity of above 600 Pascal-second. Optionally, the material isadvanced into the body using a pressure of at least 40 atmospheres orhigher, for example, 100 or 200 atmospheres or more. If the material isplastic, it may have a hardness, for example, of between 10 A shore and100 A shore and/or a Young modulus higher than 200 MPa.

In an exemplary embodiment of the invention, pressure requirements arerelaxed at a beginning of a procedure, for example, if a void is createdby bone access or by rotation of the delivery system.

In an exemplary embodiment of the invention, the outer diameter of thedelivery system is, for example, 2 mm, 3 mm, 4 mm, 5 mm or intermediateor smaller or larger diameters. Optionally, the wall thickness of thedelivery system is 0.2 or 0.3 mm. Optionally, the wall thicknessincreases towards the distal tip

It should be noted that the pressure used for delivery may depend on oneor more of: the friction between the material and the delivery system,the length of material being pushed, the pressure applied to thematerial, the pressure desired to be applied by the material to thevertebra, the manner in which the extrusion applies pressure against thevertebra, the viscosity of the material, an area of contact between thematerial and the cylinder and/or other causes of resistance to motion ofthe material.

Lower pressures may be used, for example, if it is deemed that thevertebra may be damaged or material leakage possible.

The volume injected may be, for example, 2-4 cc for a typical vertebraand as high as 8-12 cc or higher. Other volumes may be appropriate,depending for example, on the volume of space 308 and the desired effectof the injection.

In an exemplary embodiment of the invention, the rate of injection is0.25 cc/sec. Higher or lower rates may be provided, for example, between25 cc/sec and 0.1 cc/sec or less, and between 25 cc/sec and 1 cc/sec ormore. Optionally, the rate is controlled using electronic or mechanicalcircuitry. Optionally, the rate is decided by an operator responsive toexpected or imaged bone deformation in response to the pressure.Optionally, the rate is changed over the length of the procedure, forexample, being higher at a beginning and lower at an end. Optionally,the rate of injection is controlled by the operator (or automatically)responsive to a feedback mechanism, such as fluoroscopy.

Fast Setting Cement.

FIG. 15 is a plot of viscosity as a function of time for an exemplarybone cement according to the present invention. The figure is not drawnto scale and is provided to illustrate the principles of the invention.The end of a mixing process is denoted as time 0. In an exemplaryembodiment of the invention, bone cement according to the inventionenters a plastic phase upon mixing so that it has substantially noliquid phase. Optionally, mixture of polymer and monomer componentsproduces a material with viscosity of about 500 Pascal-second or morewithin 15, optionally 30, optionally 60, optionally 90, optionally 120seconds or lesser or greater or intermediate times. In an exemplaryembodiment of the invention, the material reaches a viscosity higherthan 500 Pa-s within about 30 seconds after its components mixing.Optionally, once a high viscosity is achieved, the viscosity remainsrelatively stable for 2, optionally 5, optionally 8 minutes or more. Inan exemplary embodiment of the invention, this interval of stableviscosity provides a window of opportunity for performance of a medicalprocedure. In an exemplary embodiment of the invention, stable viscositymeans that the viscosity of the cement changes by less than 200Pascal-second during a window of at least 2 minutes optionally at least4 minutes after mixing is complete. Optionally, the window begins 1, 2,3, 6, or 8 minutes after mixing is complete or lesser or intermediatetimes. In an exemplary embodiment of the invention, the viscosity of thecement remains below 1500 Pascal-second for at least 4, optionally atleast 6, optionally at least 8 optionally at least 10 minutes orintermediate or greater times.

In an exemplary embodiment of the invention, an applied injectionpressure in the cement reservoir is reduced as the cement flows throughthe cannula. Optionally, friction between the cement and the cannulawalls reduces pressure.

In an exemplary embodiment of the invention, injection of cement iscontinuous. The term continuous as used here indicates that the greatestinterruption in a flow of cement exiting a distal tip of the cannula isless than 5, optionally less than 2, optionally less than 1, optionallyless than 0.5, optionally less than 0.1 seconds or lesser orintermediate times.

In FIG. 15 the end of a mixing process is denoted as time 0. Mixing isdeemed to end when all acrylic polymer beads have been wetted withmonomer.

For purposes of comparison, the graph illustrates that an exemplaryprior art cement reaches a viscosity suitable for injection at a time ofapproximately 10.5 minutes post mixing and is completely set by about15.5 minutes.

A window of opportunity for injection with an exemplary cement accordingto the invention (Δt₁) is both longer and earlier than a comparablewindow for an exemplary prior art cement (Δt₂). Optionally, (Δt₁) beginssubstantially as soon as mixing is complete. In an exemplary embodimentof the invention, the cement has substantially no time in a liquid phasebefore entering a plastic phase.

Viscosity Measurements Over Time for Exemplary Fast Setting Cements

In order to evaluate the viscosity profile of different exemplarybatches of cement according to some embodiments of the invention, a bulkof pre-mixed bone cement is placed inside a Stainless Steel injectorbody (e.g. 2002 of FIGS. 7P and 7Q). Krause et al. described a methodfor calculating viscosity in terms of applied force. (“The viscosity ofacrylic bone cements”, Journal of Biomedical Materials Research, (1982):16:219-243). This article is fully incorporated herein by reference.

In the experimental apparatus inner diameter of injection chamber 2600is approximately 18 mm. The distal cylindrical outlet 2500 has innerdiameter of approximately 3 mm and a length of more than 4 mm. Thisconfiguration simulates a connection to standard bone cement deliverycannula/Jamshidi needle. A piston 2200 applies force (F), thus causingthe bone cement to flow through outlet 2500. Piston 2200 is set to movewith constant velocity of approximately 3 mm/min. As a result, pistondeflection is indicative of elapsed time.

The experimental procedure serves as a kind of capillary extrusionrheometer. The Rheometer measures the pressure difference from a end toend of the capillary tube. The device is made of a 18 mm cylindricalreservoir and a piston. The distal end of the reservoir consist of 4 mmlong 3 mm hole. Assuming steady flow, isothermal conditions andincompressibility of the tested material, the viscose force resistingthe motion of the fluid in the capillary is equal to the applied forceacting on the piston measured by a load cell. Results are presented asforce vs displacement. As displacement rate was constant and set to 3mm/min, the shear rate was constant as well. In order to measure thetime elapses from test beginning, the displacement rate is divided by 3(jog speed).

FIG. 16 indicates a viscosity profile of a first exemplary batch ofcement according to the invention as force (Newtons) vs displacement(mm). The cement used in this experiment included a liquid componentcontaining approximately 98.5% v/v MMA, approximately 1.5% DMPT andapproximately 20 ppm of Hydroquinone and a powder component containingapproximately 69.39% w/w PMMA, approximately 30.07% Barium Sulphate andapproximately 0.54% of Benzoyl Peroxide. The average molecular weight ofthe PMMA was approximately 110,000 Dalton. Approximately 1% of the PMMAhad a molecular weight of 700,000 to 1,000,000 Dalton. The bead size wasin the range of 10-200 microns.

In this test (Average temperature: 22.3° C.; Relative Humidity: app.48%) the cement was mixed for 30-60 seconds, then manipulated by handand placed inside injector 2002. Force was applied via piston 2200approximately 150 seconds after end of mixing, and measurements of forceand piston deflection were taken.

At a time of 2.5 minutes after mixing (0 mm deflection) the forceapplied was higher than 30 N.

At a time of 6.5 minutes after mixing (12 mm deflection) the forceapplied was about 150 N.

At a time of 7.5 minutes after mixing (15 mm deflection) the forceapplied was higher than 200 N.

At a time of 8.5 minutes after mixing (18 mm deflection) the forceapplied was higher than 500 N.

At a time of 9.17 minutes after mixing (20 mm deflection) the forceapplied was higher than 1300 N.

FIG. 17 indicates a viscosity profile of an additional exemplary batchof cement according to the invention as force (Newtons) vs displacement(mm). The cement in this test was prepared according to the same formuladescribed for the experiment of FIG. 16. In this test (Average 21.1° C.;Relative Humidity: app. 43%) the cement was mixed for approximately 45seconds, then manipulated by hand and placed inside injector 2002. Forcewas applied via piston 2200 approximately 150 seconds after end ofmixing, and measurements of force and piston deflection were taken.

At a time of 2.25 minutes after mixing (0 mm deflection) the forceapplied was higher than 30 N.

At a time of 8.25 minutes after mixing (18 mm deflection) the forceapplied was about 90 N.

At a time of 10.3 minutes after mixing (25 mm deflection) the forceapplied was higher than 150 N.

At a time of 11.4 minutes after mixing (28.5 mm deflection) the forceapplied was higher than 500 N.

At a time of 12.25 minutes after mixing (30 mm deflection) the forceapplied was higher than 800 N.

Results shown in FIGS. 16 and 17 and summarized hereinabove illustratethat exemplary bone cements according to some embodiments the inventionare ready for injection in as little as 2.25 minutes after mixing iscompleted. Alternatively or additionally, these cements arecharacterized by short mixing time (i.e. transition to plastic phase in30 to 60 seconds). The exemplary cements provide a “working window” forinjection of 4.5 to 6.3 minutes, optionally longer if more pressure isapplied. These times correspond to delivery volumes of 14.9 and 20.8 mlrespectively. These volumes are sufficient for most vertebral repairprocedures. These results comply with the desired characteristicsdescribed in FIG. 15. Differences between the two experiments reflectthe influence of temperature and humidity on reaction kinetics.

Hydraulic Material Provision System

FIG. 7A shows a delivery system 700 which is powered hydraulically. Acannula 710 is filled with material to be ejected into the body. Cannula710 is optionally detachable via a connection 712 to a body 714.Optionally, the connection is by threading. Alternatively, a fastconnection method, such as a snap connection, is used.

Body 714 converts hydraulic pressure provided via an input port 716 intoan advance of a pusher rod 708. Optionally, body 714 is integral withtube 710, but this prevents replacing tube 710 when the material to beejected is exhausted.

In an exemplary embodiment of the invention, incoming hydraulic (orpneumatic) fluid pushes against a piston 718, which advances pusher 708directly. Optionally, a hydraulic advantage is provided by the ratios ofthe piston and the pusher. Optionally, a spring 720 is provided forretracting pusher 708 when the fluid pressure is released.

Optionally, one or more spacers 722 are provided surrounding pusher 708,to prevent buckling thereof. Optionally, the spacers are mounted onspring 720. Optionally, spacers are provided at several axial locations.Alternatively to spacers, fins may extend from pusher 708 to body 714.

Optionally, in use, when material is used up, pressure is reduced,pusher 708 retracts and delivery tube 710 is replaced. Optionally, abarrel filled with material for injection, separate from tube 710 isprovided, so that tip 702 does not need to be removed from the body.

FIGS. 7B and 7C show two alternative methods of providing hydraulicpower. In FIG. 7B, a foot pedal pump 740 is used, in which a user placeshis foot on a pedal 744 and depresses it against a plate 742. Variousfoot pumps are known in the art. Optionally, a long press releases thepressure. Optionally, the hydraulic subsystem is a sealed system whichis provided ready to use (e.g., including fluid) to the user and/ordistributor. Exemplary lengths of the flexible tubing are between 0.2and 3 meters, for example, between 1 and 2 meters. However, greaterlengths can be used as well.

In an exemplary embodiment of the invention, a foot operable actuatoremploys a 1.5 m, optionally 2 m, optionally 2.5 m tube or a tube oflesser or intermediate or greater length (see FIG. 7B).

In an exemplary embodiment of the invention, a hand operable actuatoremploys a 0.25 m, optionally 0.5 m, optionally 1.0 m tube or a tube oflesser or intermediate or greater length.

Also shown in FIG. 7B is a variant of body 714, indicated as 714′.Instead of a single spring 720, two springs 720′ are shown, with thespacer(s) between the springs. Optionally, the use of multiple springshelps maintain the spacers near a middle (or other relative length unit)of the pusher in danger of buckling.

FIG. 7C shows an alternative embodiment, in which a hand pump 760 isused, which pump can be of any type known in the art, for example, amechanism 762 comprising a piston 764 and a cylinder 766. Optionally,the pumping is by rotating piston 764 elative to cylinder 766, whichcomponents include matching threading. Alternatively, linear motion isused. Optionally, a hydraulic gain is achieved between the pump and thedelivery mechanism, for example a gain of 1:3, 1:5, 1:10 or any smaller,intermediate or greater gain.

In an exemplary embodiment of the invention, the hydraulic system isprovided as a disposable unit, with a non-disposable (or a disposable)foot pump.

FIG. 7D shows a disposable mixing and storage chamber 770 and FIG. 7Eshows a reusable pump 750 with a disposable hydraulic capsule 754.

Referring to FIG. 7D, a same capsule 770 is optionally used both formixing and for storage/delivery of a material. Optionally, the materialis a setting cement such as PMMA. In the embodiment of a hydraulicdelivery stream, a flexible tube 772 is optionally permanently connectedto a pump (FIG. 7E). When fluid is provided through tube 772, a piston774 moves through a cylinder volume 776 and pushes the material out(e.g., and into a delivery system). In the figure, the capsule is shownloaded with a mixer 778. Optionally, materials are provided into volume776 using a detachable funnel (not shown) and then the funnel is removedand mixer 778 inserted instead. In the exemplary mixer shown, a cap 782covers cylinder 776. When mixing is completed, this cap may be replacedby a fitting adapted to couple to the delivery tube.

In use, a handle 780 is rotated, rotating a shaft 786 having a rotor 788defined thereof, for example, as a helix. An optional stator 789 isprovided. An optional vent 784 may be connected to a vacuum source, tosuck out toxic and/or bad smelling fumes caused by the setting of thematerial. Optionally, a viscosity of the materials is estimated by thedifficulty in turning the handle. Optionally, the handle includes aclutch (not shown) that skips when a desired viscosity is reached.Optionally, the clutch is settable. Optionally, a viscosity meter isused or viscosity is estimated based on temperature, formulation andtime from mixing.

Cap 782 optionally includes a squeegee or other wiper, to wipe materialoff of mixer 778 when it is removed from capsule 770.

Referring to FIG. 7E, tube 772 connects to a capsule 754 which includesa piston 798 and a volume 797, pre-filled with fluid. In an exemplaryembodiment of the invention, a frame 756 is provided attached to pump750 for selectively receiving capsule 754.

Pump 750 is, for example, a hydraulic oil based pump-mechanism 752 thatextends a pushing rod 795 which advances piston 798.

In the embodiment shown, a foot pedal 758, attached to an axis 791,forces a piston 755 into a cylinder 792. A one way valve 794 allows thefluid in cylinder 792 to flow into a volume 749 where it pushes againsta piston 757. When pedal 758 is released, a spring (not shown) pulls itback to an upward position and allows a hydraulic fluid to flow from astorage chamber 759 (e.g., which surrounds the pump) through a one wayvalve 793 into cylinder 792.

A pressure relief valve 751 is optionally provided to prevent overpressurizing of cylinder 749. In an exemplary embodiment of theinvention, a spring 796 is provided to push back piston 757 and pusher795 with it, when pressure is released. Optionally, pressure is releasedusing a bypass valve 753, which is manually operated. Once pusher rod795 is retracted, capsule 740 is optionally removed.

FIGS. 7F (side view) and 7G (cross section) illustrate a hydraulicdelivery system 2000, comprising a reservoir 2002 for material (e.g.bone cement) and a pressure source 2004. Optionally a flexible tube 2006which connects reservoir 2002 and pressure source 2004 is included insystem 2000. Reservoir 2002 is connectable to a cannula 2008. Cannula2008 can optionally be introduced into a bone prior to injection ofmaterial from reservoir 2002. Reservoir 2002 and cannula 2008 may beconnected using, for example, a luer lock connector 2010 and/or threadedconnector 2014. Alternately, reservoir 2002 and cannula 2008 may befashioned as a single piece. Optionally, cannula 2008 is compatible witha stylet (not shown).

In an exemplary embodiment of the invention, cannula 2008 is aplastically deformable cannula, optionally a slitted cannula.Plastically deformable cannulae in general, and slitted cannulae inparticular are described in detail in co-pending U.S. application60/721,094 entitled “Tools and Methods for Material Delivery into theBody”, and in co-pending application entitled “Cannula” and filedconcurrently with the instant application, the disclosures of which arefully incorporated herein by reference. Optionally, use of a plasticallydeformable cannula 2008 facilitates positioning of reservoir 2002outside of an X-ray imaging field.

In an exemplary embodiment of the invention, pressure source 2004 is ahydraulic pressure source. Pressure source 2004 may be filled with anyliquid. In an exemplary embodiment of the invention, pressure source2004 is filled is filled with a sterile liquid 2026 (FIG. 7G), such assaline or water. Optionally, filling is via flexible tube 2006.Optionally, an outlet of tube 2006 is immersed in the liquid, andhydraulic actuator 2012 is operated to fill pressure source 2004 withliquid. In the exemplary embodiment of FIGS. 7F and 7G, the actuator isdepicted as a ball screw connection 2013 equipped with a rotating handle2012. According to this embodiment, handle 2012 is rotated to fillpressure source 2004 with liquid.

In an exemplary embodiment of the invention, pressure source 2004 isprovided as a prefilled unit. Optionally the prefilled unit includesbody 2004, tube 2006 and/or cap 2013 and/or handle 2012 with drive shaft2022. Optionally the prefilled unit includes body 2004, optionally withtube 2006 and is provided with temporary seals at each end. In anexemplary embodiment of the invention, the seals are removed or brokenwhen additional system components are connected.

Although an exemplary manually operable actuator is pictured, hydraulicactuator 2012 may be operable by, for example, a foot pedal (see FIG. 7Udescribed hereinbelow) or an electric actuator, such as a linearactuator or a motor. Electric operation may be achieved, for example, byemploying a battery (as described hereinbelow) and/or mains supply. Inan exemplary embodiment of the invention, the hydraulic actuator causespressures source 2004 to generate a pressure of 50, optionally 100,optionally 150, optionally 200, optionally 300 atmospheres or lesser orgreater or intermediate values.

Optionally, a safety mechanism (described in greater detail hereinbelow)limits pressure. In an exemplary embodiment of the invention, the safetymechanism includes a valve with a defined pressure threshold. In anexemplary embodiment of the invention, the threshold is set to preventinjection of cement after it has solidified and/or to protect the systemfrom being damaged by attempts to inject solidified cement.

For example if a particular cement formulation is flowable at a pressureof 150 atmospheres during the “working window”, a valve threshold may beset at 170 atmospheres. In such a case, the system would be designed towithstand a greater internal pressure, such as 200 atmospheres. Thisarrangement reduces the chance that the system will be damaged whencement solidifies.

Optionally, the pressure threshold is 150 or 210 atmospheres or lesseror greater or intermediate values. In an exemplary embodiment of theinvention, the safety mechanism may be used to release trapped gases(e.g. air) and/or cement. In an exemplary embodiment of the invention,each activation of the hydraulic actuator (e.g., handle rotation, footpedal pressing) results in injection of defined amount of cement.Optionally, the hydraulic actuator provides pressure amplification.

Optionally, air is removed from pressure source 2004 and/or tube 2006prior to connection of pressure source 2004 to reservoir 2002. One ormore connectors 2016 can be optionally employed to connect of reservoir2002 to pressure source 2004, optionally via tube 2006. Connectors 2016may be, for example, luer lock connectors, quick release connectors orthreaded connectors.

In an exemplary embodiment of the invention, delivery system 2000 isemployed to deliver a viscous material, optionally a viscous bonecement. In an exemplary embodiment of the invention, cement components(e.g. powder and liquid) are mixed. The mixture is loaded into reservoir2002, optionally via a reservoir cap 2014. Optionally cap 2014 isunscrewed and reservoir 2002 is filled with bone cement 2020 (FIG. 7G).According to various embodiments of the invention, cement 2020 may beinserted into reservoir 2002 manually or by use of a tool or fillingdevice. In an exemplary embodiment of the invention, cement 2020 issufficiently viscous that it may be preformed to a size and shape whichpermit easy insertion into reservoir 2002. After cement 2020 is insertedin reservoir 2002, cap 2014 is replaced. Pressure source 2004 isconnected to reservoir 2002, optionally via flexible tube 2006, viaconnector(s) 2016. In an exemplary embodiment of the invention, pump2004, tube 2006, connector 2016 and fluid 2026 are provided as apre-assembled sterile unit. Optionally, air is removed from the systemvia a pressure release valve 2017, optionally on connector 2016.Optionally rotation of handle 2012 increases pressure in the system anddrives air out. Optionally, air is released through valve 2017 or isexpelled via cannula 2008 prior to insertion of the cannula in the body.

Optionally, mixing of cement components is performed under vacuum toprevent air bubbles from being entrapped in the cement.

Reservoir 2002 is connected to cannula 2008 via connector 2010. In anexemplary embodiment of the invention, connector 2010 serves as anorientation marker which indicates an ejection direction of cementinjected through the cannula. Operation of handle 2012 delivers cement2020 from reservoir 2002 to cannula 2008. In an exemplary embodiment ofthe invention, rotation of handle 2012 rotates pump thread 2022 andadvances piston 2024. Advancing piston 2024 applies pressure to liquid2026 within pressure source 2004 and causes liquid 2026 to advance intoreservoir 2002, optionally via tube 2006. Liquid 2028 in reservoir 2002applies pressure to a piston 2018 within reservoir 2002. As piston 2018advances through reservoir 2002, it causes cement 2020 to advance andexit reservoir 2002 via the cannula 2008.

According to various embodiments of the invention, 2008 cannula may beequipped with one or more apertures for cement delivery. Optionally,these apertures are located at a distal end and/or near the distal endof cannula 2008. Optionally, the apertures face axially and/or radiallywith respect to the cannula. Optionally, the cannula distal end isclosed. In an exemplary embodiment of the invention, one or more lateralopenings on the cannula permit sideways injection to a desired target ina bone from a cannula with a permanently closed distal tip.

In an exemplary embodiment of the invention, the injection procedure ismonitored by a medical imaging system (e.g. fluoroscopy). When a desiredamount of cement 2020 has been delivered through cannula 2008, injectionis stopped. Optionally, reservoir 2002 is disconnected from cannula 2008and/or tube 2006 and/or pressure source 2004. Cannula 2008 is removedfrom the bone, and the operation site is closed.

In an exemplary embodiment of the invention, cannula 2008 and/or cement2020 are composed of biocompatible materials. In an exemplary embodimentof the invention, components of system 2000 which contact cement 2020are not adversely affected by the cement. For example if MMA is employedas a component of the cement, reservoir 2002 may be constructed of anMMA monomer resistant polymer/Plastic while cannula 2008 may beconstructed of Stainless Steel. In various exemplary embodiments of theinvention, reservoir 2002 may be made of, for example, nylon, pressuresource 2004 may be made of, for example, metal and/or plastic (e.g.polycarbonate), and the flexible tube 2006 is made of, for instance,nylon or Teflon®.

In an exemplary embodiment of the invention, reservoir 2002 and/orpressure source 2004 are constructed of Amorphous Nylon (e.g. Nylon Nos.6, 6/6 or 12, e.g. Grilamid 90 or Durethan) and/or of a Cyclic OlefinCopolymer (COC) (e.g., Topas®; Ticona GmbH, Kelsterbach, Germany). Thesematerials are resistant to cement components, including the monomercomponent.

In an exemplary embodiment of the invention, the reservoir 2002 isdesigned to withstand pressures in the range of 100 to 300 atmospheres.Optionally, a reservoir with an internal diameter of 18 mm wisconstructed with a wall thickness of 5 mm so that the outer diameter is28 mm. Optionally, the walls are ribbed to increase strength and/orreduce weight.

The pressure source 2004 will come in contact only with the hydraulicfluid, such as water or a saline solution. Optionally, pressure source2004 is constructed of Polycarbonate and/or polysulphone and/or PEEK orother materials which are not corroded by the hydraulic fluid.

Optionally, system 2000 employs a pressure of at least 100, optionally150, optionally, optionally 200, optionally 300 atmospheres or lesser orintermediate or greater values to inject cement 2020. In an exemplaryembodiment of the invention, system 2000 is constructed to withstandthese operational pressures. The actual pressure which accumulates inthe system may vary, for example as the viscosity of cement 2020 varies.Various types of connectors and/or pressure sources and/or reservoirsand/or cannulae may be employed depending upon an anticipated pressure.One of ordinary skill in the art will be able to select commerciallyavailable components such as connectors, tubing and O-rings which aresuitable for use in construction of a system 2000 with a givenanticipated operating pressure. In some exemplary embodiments of theinvention, pressure is provided by a tamping instrument including a rodadapted to comply with a lumen of the cannula (see FIG. 7A). In otherexemplary embodiments of the invention, pressure is provided by a piston(e.g. 2018 in FIG. 7G) with a diameter wider than the cannula lumen.

It is stressed that the combination of high viscosity cements employedin the context of the invention and the small diameter of the cannula tobe filled renders standard syringes or other non-amplifying pressuresources ill suited for cannula filling. Optionally, the viscous cementis manually manipulated to facilitate loading of the delivery devicereservoir as described hereinbelow under “Transfer of viscousmaterials”.

In those embodiments of the invention in which a tamping rod isemployed, it may optionally be introduced into the vertebra via aworking sleeve characterized by a slightly larger diameter than thecannula diameter.

Optionally, reservoir 2002 is transparent to permit visualization ofcement 2020. In an exemplary embodiment of the invention, a transparentreservoir 2002 is marked with graduations indicating the amount cement2020 in the reservoir. Optionally, this permits a user to ascertain howmuch cement is being injected.

In an exemplary embodiment of the invention, pressure source 2004,optionally attached to tube 2006, are provided filled with liquid.Optionally, air has already been flushed from these components. Such anembodiment may expedite operating room procedures. According to thisembodiment, a quick connector 2016, connecting the reservoir 2002 to theflexible tube 2006, is equipped with a uni-directional valve 2017 thatseals the tube 2006 until it is connected to the reservoir 2002.

Optionally, a uni-directional valve (not shown in the Figures) isincorporated into the reservoir piston 2018, and is opened/releasedtoward reservoir portion that does not contain cement 2028. For example,systems of the type illustrated in FIG. 7G, the cement is loaded from adistal side (covered by cap 2014) of container 2002. Prior to attachingconnector 2016, air can be drained by a one-way valve in piston 2018, soentrapped air can flow from container 2020 through the one-way valve inpiston 2018, and through escape valve 2017.

In an exemplary embodiment of the invention, (FIGS. 7 p; 7S) air escapesfrom opening 2500 directly. Optionally, no valves are provided.

Although a hand operated handle is pictured, according to additionalexemplary embodiments of the invention, handle 2012 may be replaced by afoot pedal that is used to actuate piston 2024. Alternatively oradditionally, pressure source 2004 may rely upon electric power foractuation. Electric power may be supplied, for example, by a battery. Inan exemplary embodiment of the invention, a battery powered motor turnsscrew threads 2022 to advance piston 2024.

The construction and operation of exemplary hydraulic pressure sourcesfor use in systems of the general type depicted in FIGS. 7F and 7G isdepicted in greater detail in FIGS. 7I through 7O.

Exemplary Pressure Source

FIG. 7I illustrates a hydraulic pressure source 2004 including anactuation handle 2012 connected to a drive shaft 2050 and piston 2060.Drive shaft 2050 passes through hydraulic chamber cap 2013 and isinsertable in hydraulic pressure body 2005. Piston 2060 is connected to,or constructed as part of, a distal end of drive shaft 2050. Piston 2060forms a circumferential seal with respect to an inner surface of a lumenof hydraulic pressure body 2005. In an exemplary embodiment of theinvention, hydraulic pressure body 2005 is constructed of AmorphousNylon or Polycarbonate.

In an exemplary embodiment of the invention, a small step of thethreading (eg 1 mm/rotation), a small radius of bolt (eg 4 mm) andmaterials employed in construction for bolt and nut (eg Nylon for nut2013 and stainless steel for bolt 2050) produce a low frictioncoefficient.

Amorphous Nylon provides the requisite strength to resist high internalpressures with a low weight when compared to previously available steelhydraulic pressure sources. In an exemplary embodiment of the invention,an amorphous nylon reservoir with an OD 0f 20, optionally 25, optionally30, optionally 35 mm (or lesser or intermediate or greater values)resists an internal pressure of as much as 300 atmospheres or more.Optionally, it can be transparent. Optionally, a transparent pressurebody 2005 allows an operator to observe progress of piston 2060. In anexemplary embodiment of the invention, progress of the piston is gaugedagainst calibration markings on body 2005.

In an exemplary embodiment of the invention, pressure body 2005 isconnectable to a flexible tube 2006. Optionally, tube 2006 is glued toreservoir 2002 directly (eg by UV curing glue). The inset 2019 shows anexemplary embodiment of this connection in greater detail. A funnel 2055is seated in a distal aperture of hydraulic pressure body 2005 andsealed by means of an O-ring 2052 and adapter plug 2051. According tothis exemplary embodiment of the invention, as pressure on hydraulicfluid in hydraulic pressure body 2005 increases, funnel 2055 is morefirmly seated against the distal aperture of hydraulic pressure body2005. Optionally, this arrangement spreads the stresses radially over adistal end of the reservoir. Optionally, this arrangement prevents leaksat operating pressures of 100 to 300 atmospheres. The liquid is forcedthrough tube 2006 as the pressure increases. In an exemplary embodimentof the invention, a hydraulic unit including body 2005, cap 2013, driveshaft 2050 and piston 2060 is provided as a unit pre-filled with asterile liquid. Optionally, walls 2005 are transparent so that piston2060 is visible to an operator of the unit. In an exemplary embodimentof the invention, transparent walls 2005 are marked with graduationswhich indicate an injected volume of cement.

In an exemplary embodiment of the invention, specific materials for thecover 2013 and drive shaft 2050 are chosen to reduce the frictioncoefficient (μ). Optionally, cover 2013 is made of a polymer/plasticwhile shaft 2050 is made of steel. Optionally, Radius of Friction (R) isreduced by reducing the thread diameter on shaft 2050 and/or cap 2013.M=R·ff=μ·F

So M=R*μ*f. Therefore, a reduction in the moment the moment needed forevery normal force F is optionally achieved by reducing R and/or μ.

Working moment (M) is the product of R and the radial force (f) of thehydraulic liquid. The force (F) between cap 2013 and shaft 2050 is theaxial force applied on the piston 2060.

FIG. 7J is an exploded view of a handle and piston assembly as depictedin the exemplary embodiment of FIG. 7I. According to this embodiment,pins 2053 anchor handle 2012 to drive shaft 2050. Optionally pins 2053are designed to break if excessive torque is applied. In an exemplaryembodiment of the invention, breaking of pins 2053 is a safety feature.Cap 2013 and shaft 2050 are each threaded so that rotation of handle2012 can cause shaft 2050 to advance or recede through cap 2013.Optionally, cap 2013 is constructed of a plastic polymer. Optionally,shaft 2050 is constructed of metal, for example stainless steel. In anexemplary embodiment of the invention, threaded shaft 2050 isconstructed of stainless steel and has a diameter of 6 mm, optionally 5mm, optionally, 4 mm or lesser or greater or intermediate diameters.Optionally, stainless steel threads mated to plastic polymer threadsprovide a low friction connection which makes it easy to operate handle2012 manually. In an exemplary embodiment of the invention, a narrowdiameter drive shaft 2050 is employed as a means of reducing the amountof friction against threads of cap 2013. In an exemplary embodiment ofthe invention, threads on shaft 2050 and 2013 each engage a set of ballbearings to provide a ball screw mechanism. In this figure, an optionalpressure release port 2070 on piston 2060 is visible.

FIG. 7K is a cross sectional view of a handle and piston assembly asdepicted in FIG. 7J FIG. 7K shows a second set of threads 2057 on cap2013. Threads 2057 are one exemplary means to engage cap 2013 tohydraulic pressure body 2005. Once cap 2013 is engaged to hydraulicpressure body 2005, operation of handle 2012 will cause advancement ofpiston 2060 in hydraulic pressure body 2005. Optionally, threads 2057are in the same direction, as threads on shaft 2050 to preventdisassembly. Optionally, threads 2057 are locked once the cap 2013 iscompletely on.

FIG. 7K also shows an exemplary engagement mechanism by which driveshaft 2050 may be coupled to piston 2060. The pictured engagementmechanism relies upon a ball 2058 which snaps into a matching socket(2059; FIG. 7M) in piston 2060. In an exemplary embodiment of theinvention, this arrangement assures that piston 2o60 remains attached toball 2058 as shaft 2050 advances. Optionally, a ball/socket connectionof this type permits piston 2060 to advance without rotating as bolt2050 rotates. In an exemplary embodiment of the invention, this lack ofpiston rotation increases valve life and improves sealing. Optionally,the ball/socket type connection provides a sufficiently strongengagement force so that back turning of shaft 2050 will retract piston2060. Optionally, a ball socket connection is economical yet reliable.

In an exemplary embodiment of the invention, operation of handle 2012 inan opposite direction will cause retreat of piston 2060 in hydraulicpressure body 2005. Optionally, operation in a reverse direction ceasesinjection of cement.

Pressure Source Safety Valve

FIG. 7L is an exploded view of a piston 2060 including a pressurerelease valve which can relieve excess pressure of hydraulic fluid byventing hydraulic fluid through one or more release ports 2070 on piston2060. In an exemplary embodiment of the invention, the pressure reliefvalve includes a spring 2062, a pressure release aperture element 2064,and a sealing gasket 2067. In the figure, optional washers 2065, 2066,2068 and 2069 are depicted. In an exemplary embodiment of the invention,the pressure release valve is triggered at a pressure of 160Atmospheres. Optionally, a threshold pressure of 160 atmospheresprotects a system designed to withstand 200 atmospheres.

FIGS. 7M and 7N are cross sectional views of the valve of FIG. 7L in anopen and a closed operational state respectively. FIG. 7N shows spring2062 in a fully extended configuration. As distal end 2058 of drivemechanism is forced into receptacle 2059, piston 2060 advances throughhydraulic pressure body 2005. Advancement of piston 2060 causes anincrease in pressure of a fluid residing in hydraulic pressure body2005. Advancement of piston 2060 causes an increase in pressure of afluid residing in hydraulic pressure body 2005. When the pressure insidethe hydraulic pressure body 2005 reaches a predetermined threshold(e.g., 150, 160 or 210 atmospheres), the retraction of spring 2062causes apertured element 2064 to protrude through seal 2067. Aperturedelement 2064 provides a channel of fluid communication betweenpressurized fluid 2020 (FIG. 7G) and lower pressure compartment (2028).This permits hydraulic fluid to flow to the rear chamber 2028 behindpiston 2060 via release ports 2070. Release of hydraulic fluid causesthe pressure to drop below the threshold, spring 2062 to expand and sealthe valve. In an exemplary embodiment of the invention, releasedhydraulic fluid is visible in transparent pressure body 2005.

FIG. 7O is a side view of an exemplary embodiment of piston 2060 showingrelease port 2070. In an exemplary embodiment of the invention, openingof the valve reduces the hydraulic pressure to the threshold pressure.

In an exemplary embodiment of the invention, pressure at the definedthreshold, indicates that the procedure should be stopped because thecement has solidified. If the physician wants to continue with theprocedure, replacement of reservoir 2002 is indicated.

Injection Reservoir

FIGS. 7P and 7Q are side cross-sectional views of an injection reservoir2002 according to an exemplary embodiment of the invention. Reservoir2002 may be constructed of, for example, amorphous nylon e.g. Durethan®(LANXESS, Leverkuzen, Germany), Grilamid® (EMS-Grivory,Reichenauerstrasse, Switzerland) or Topas® (Ticona GmbH, Kelsterbach,Germany). In an exemplary embodiment of the invention, materials forconstruction of reservoir 2002 are selected so that they are notcorroded by the relevant cement. In an exemplary embodiment of theinvention, the amorphous nylon is transparent. In an exemplaryembodiment of the invention, the thickness of walls 2003 of reservoir2002 is greater than 3 mm, optionally greater than 4 mm, optionallygreater than 5 mm optionally greater than 6 mm or intermediate orgreater values. In an exemplary embodiment of the invention, reservoir2002 is characterized by a wall thickness to internal diameter ratio ofabout 0.23, optionally 0.25, optionally, 0.27, optionally 0.29 (e.g.,wall thickness of about 5 mm and ID of about 18 mm), This ratio providessufficient strength to withstand pressures of 100 to 300 atmospheres.

In an exemplary embodiment of the invention, walls 2003 of reservoir2002 are transparent and marked with a scale indicating volume.Optionally, this permits an operator of the system to ascertain how muchcement has been injected at any given moment. Optionally, ribs providedto add strength serve as a scale indicating volume.

In an exemplary embodiment of the invention, cement reservoir 2002 isloadable with sufficient cement to treat at least one vertebra with asingle injected aliquot. Optionally, 5 ml optionally 10 ml orintermediate or greater volumes are typically employed to treat a singlevertebra. Optionally, cement reservoir 2002 is loadable with sufficientcement to treat at least two vertebrae, optionally at least 3,optionally at least 4 vertebrae without re-filling. Optionally, thisreduces a number of access procedures for each vertebra, optionally to asingle access procedure. In an exemplary embodiment of the invention, asingle access procedure is employed to treat at least two locations in avertebra.

In an exemplary embodiment of the invention, reservoir 2002 is loadedwith a cement characterized by a long “working window” during which thecement is characterized by a viscosity above 500 Pascal second but isnot yet solidified. Optionally, the working window is greater than 5,optionally 8, optionally 12, optionally 15 minutes or intermediate orgreater times.

In an exemplary embodiment of the invention, reservoir 2002 serves alsoas a mixing chamber. Optionally, a polymer component and a monomercomponent of the cement are mixable in reservoir 2002. Alternatively,mixing is performed in a separate mixing apparatus and cement istransferred to the reservoir after mixing is complete.

Reservoir Assembly

FIG. 7P illustrates assembly of an exemplary injection reservoir forinjection of bone cement. While this reservoir is suited for use in asystem of the general type depicted in FIGS. 7F and 7G, the exemplaryembodiment of FIG. 7P features a proximal reservoir cap 2100 as opposedto the distal reservoir cap of FIGS. 7F and 7G.

A reservoir cap 2100 includes a connector plug 2110 equipped with a tubeconnection 2310 to facilitate connection to tube 2006 which containshydraulic fluid. Plug 2110 and tube connection 2310 form a contiguouslumen 2300 which facilitates delivery of hydraulic fluid from tube 2006.Plug 2110 optionally rotates within cap 2100 so that an angle of tubeconnection 2310 with respect to reservoir 2002 can be adjusted.

In an exemplary embodiment of the invention, the angle of connection2310 with respect to reservoir 2002 is adjusted so that tube 2006 is outof the field of view of an X-ray imaging device. In an exemplaryembodiment of the invention, rotation of plug 2110 makes connection of2006 more convenient. Plug 2110 optionally includes a coupling portion2115 which mates with a complementary coupling portion 2215 (FIG. 7Q) ondelivery piston 2200. Optionally, piston 2200 is mounted on plug 2110during assembly by snap coupling portions 2115 and 2215.

Cement reservoir 2600 is optionally filled with cement prior to closingof reservoir body 2003 with cap 2100. Cap 2100 can then be attached tobody 2003 by means of, for example, mated threads on the two pieces. Atthis stage, both plug 2100 and piston 2200 are sealed to an inner sideof walls 2003, for example by O-rings 2211. During operation, hydraulicactuator 2004 causes a fluid to flow through tube 2006 under pressureand enter lumen 2300. As the applied pressure increases, this fluidaccumulates in portion 2700 of reservoir 2002 (FIG. 7Q). In an exemplaryembodiment of the invention, plug 2100 and piston 2200 disengage whenthe fluid pressure developed in 2700 supplies enough force to advancepiston 2200 against resistance supplied by cement in portion 2600 ofreservoir 2002.

At the distal end of reservoir 2002, an optional inner plug 2400 engagesan outer connector 2410 and holds outer connector 2410 to the distal endof the injection reservoir. Outer connector 2410 is constructed toengage an injection cannula and to remain engaged at a relevantoperating pressure of the delivery system. Inner plug 2400 and outerconnector 2410 form a channel of fluid communication 2500 which canfacilitate a flow of cement from reservoir 2600 to an inner lumen of acannula connected to connector 2410. The function of plug 2400 duringfilling of reservoir 2002 is described with regard to FIGS. 7R and 7S,hereinbelow.

FIG. 7Q shows that fluid 2700 accumulates within 2005 and pushes piston2200 away from plug 2110 and towards plug 2400. As the volume of fluid2700 increases, the volume of cement 2600 decreases and the cement ispushed outwards through channel 2500 into a cannula (not shown in thisfigure). In an exemplary embodiment of the invention, piston 2200 is afloating piston which is moved by a column of fluid 2700. Optionally,walls 2005 are transparent so that piston 2200 is visible to an operatorof the unit, for example as an indicator of cement volume. In anexemplary embodiment of the invention, transparent walls 2003 are markedwith graduations which indicate an injected volume of cement.

In an exemplary embodiment of the invention, cement reservoir 2600 issupplied as a separate unit comprising walls 2003, inner plug 2400 (FIG.7R) and outer connector 2410. FIGS. 7R and 7S illustrate one embodimentof this exemplary type. Plug 2400 contains an aperture 2500 which isinitially covered by connector 2410 during filling of the reservoir withcement and subsequently opened to permit attachment of a cannula.

FIG. 7R illustrates outer connector 2410, inner plug 2400 and walls 2003in cross section. In this figure, connector 2410 is only partiallypressed onto a protruding portion of plug 2400. Seal 2508 remainsunbroken. O-ring 2411 provides a tight seal between walls 2003 and plug2400. This arrangement permits introduction of cement into the reservoirfrom a proximal end before cap 2100 (FIG. Q) is attached. Once thereservoir is filled, cap 2100 may be applied as described above.Optionally, this arrangement permits a more efficient seal to a cannulaand/or provides the possibility to rotate the cannula with respect tothe reservoir In an exemplary embodiment of the invention, the cannulamay be deformed from a straight line and/or be directional.

Once the reservoir is filled and capped, seal 2508 may be broken (FIG.7S) by advancing connector 2410 towards plug 2400. Breaking of seal 2508creates channel of fluid communication 2500 which can facilitate a flowof cement outwards from the reservoir into a cannula (not shown in thisfigure) connected to connector 2410. In an exemplary embodiment of theinvention, breaking of seal 2508 exposes a threaded and/or luerconnection which is adapted to engage a cannula.

FIG. 7T depicts an exemplary embodiment of reservoir 2600 in which walls2003 are formed as a contiguous unit which includes some of thefunctional characteristics of outer connector 2410, inner plug 2400 inFIG. 7S. In the exemplary embodiment of FIG. 7T, aperture 2500 is notsealed. Walls 2003 include threads 2509 and/or luer connector 2510 forattachment to a cannula.

Foot Operable Actuator

FIG. 7U is a perspective view of a foot operable hydraulic actuator4004. A foot operable actuator may be used in place of a hand operableactuator. In an exemplary embodiment of the invention, a foot operatedactuator permits an operator to employ both hands for other tasks and/orreduces the need for an assistant. In the figure, hydraulic reservoir4005 is functionally similar to hydraulic reservoir 2005 as describedhereinabove. Locking ring 4013 is functionally analogous to reservoircap 2013 as described hereinabove. The pictured foot operable actuatorcontains a drive pedal 4100 which moves angularly with respect to anaxle 4300. Each depression advances a hydraulic piston in hydraulicreservoir 4005 by a fixed increment. After pedal 4100 is depressed foractuation, it returns to a pre-actuation position automatically. Thisreturn may be achieved, for example, by use of a spring which provides aresistive force. Optionally, actuator 4004 includes an additional pedal4200 for pressure release which moves angularly with respect to an axle4300. In an exemplary embodiment of the invention, pedals 4100 and 4200are clearly marked so that an operator can distinguish between themeasily. Markings may be, for example, in printed symbols and/or by pedalcolor and/or by pedal size and/or by pedal shape and/or by pedalposition.

In an exemplary embodiment of the invention, walls of hydraulic pressurechamber 4005 are transparent and marked with a scale. Optionally, thescale indicates indicating volume. Optionally, this permits an operatorof the system to ascertain how much cement has been injected at anygiven moment. Optionally, ribs provided in the walls to add strengthserve as a scale indicating volume.

Pressure inducing levers may apply increments of hydraulic pressureusing any clutch/drive mechanism known in the art to advance a hydraulicpiston within hydraulic reservoir 4005. Examples of suitable drivemechanisms include, but are not limited to ratchet pawl mechanisms,sprag clutches, roller ramp clutches and mechanical diodes, camfollowers and roller bearing cam followers. Sprag clutches arecommercially available (e.g. from JTEKT Co.; Osaka/Nagoya; Japan).Mechanical diodes are available from, for example, Epilogics (Los Gatos;CA; USA). One of ordinary skill in the art of mechanical engineeringwill be able to select a suitable commercially available drivemechanism, or construct a suitable drive mechanism from commerciallyavailable parts in consideration of desired performance characteristicsfor any particular contemplated embodiment of the invention.

In an exemplary embodiment of the invention, release pedal 4200 isprovided to release some or all applied hydraulic force. Such a releasemay be desired, for example to change or replace cement reservoir 2004,at the end of a surgical procedure and/or in the event of an emergency.Optionally, release pedal 4200 may open a valve which vents hydraulicfluid from reservoir 4005. Alternatively or additionally, release pedal4200 may act by permitting a threaded drive shaft to move backwards sothat a hydraulic piston in reservoir 4005 is retracted.

FIG. 7V illustrates one exemplary embodiment of a pedal operated drivemechanism with a companion release pedal.

When drive pedal 4100 is depressed by a foot, it rotates with respect toaxle 4300 and depresses drive arm 4130. Drive arm 4130 engages gear 4140causes it to rotate angularly by a single increment. The increment maybe varied by varying the number of teeth on gear 4140. Gear 4140 ismounted on a drive nut 4150 so that rotation of gear 4140 causesrotation of drive nut 4150. Drive nut 4150 is equipped with an innerthreading mechanism (not visible in the figure) which can advancedriveshaft 4230 without rotating a distal end thereof. As drive nut 4150is rotated it operates the inner threading mechanism and drives driveshaft 4230 outwards through a narrow portion 4225 of a hole in clutchplate 4220. Drive arm 4130 and gear 4140 are depicted to generallyindicate the presence of a ratcheted gear or functionally similarmechanism and their pictured shapes should not be viewed as a limit ofthe invention.

When drive pedal 4100 is released, it is raised by a spring (not shown).Drive arm 4130 disengages from gear 4140. Drive arm axle 4120 permitsdrive arm 4130 to rotate slightly as it is raised and lowered so that itdisengages and re-engages teeth of gear 4140.

A distal end of drive shaft 4230 pushes a piston (not shown in thisview) in hydraulic pressure reservoir 4005 (FIG. 7U). Pressure in thereservoir tends to force drive shaft 4230 to return towards drive nut4150.

A narrow aperture 4225 in clutch plate 4220 prevents rotation of driveshaft 4230 while drive arm 4130 is disengaged from gear 4140 andprevents the shaft from retuning towards nut 4150. Clutch plate 4220 isoptionally attached to pedal 4200 by rod 4210 and pin 4215.

When release lever 4200 is depressed, it lowers clutch plate 4220 soshaft 4230 passes through a wide portion 4227 of the hole. Shaft 4230 isthen free to retract towards nut 4150 because it can rotate in wideportion 4227 of the hole. Optionally, shaft 4230 is constructed withsectorial threading (not pictured in this view) so that when clutchplate 4220 descends shaft 4230 rotates against a nut that defines adesired resistance.

Optionally, operation of lever 4200 releases all of the pressure in thesystem or only a portion of it. Optionally, release may be sudden orgradual.

FIG. 7W illustrates a foot operable hydraulic actuator as seen in FIG.7U with hydraulic reservoir 4005 removed. In this view, drive shaft 4230is characterized by optional sectorial threading 4231. Shaft 4230 ispictured in wide portion 4227 of a hole in clutch plate 4220 so that itcan retract. A distal end of shaft 4230 is fitted with a piston 2200. Asshaft 4230 advances it drives piston 2200 into pressure reservoir 4005(not pictured in this view) and increases the hydraulic pressure.

FIG. 7X is a cross sectional view of the exemplary actuator depicted inFIG. 7W. In this view release lever 4200 is raised so that wide portion4227 of the hole in clutch plate 4220 is raised off of sectorial threads4231 on shaft 4230. This causes the clutch plate to engage the driveshaft and prevent retraction of the drive shaft.

FIG. 7Y illustrates an exemplary embodiment of drive nut 4150 adapted toengage and rotate sectorial threads such as those illustrated in FIGS.7W and 7X.

FIG. 7Z is a perspective view of the exemplary foot activated actuatordepicted in FIGS. 7W, 7X, and 7Y from below. This view illustratesclearly a housing 4155 of the inner threading mechanism which advancesshaft 4230 by engaging and turning sectorial threads 4231.

Additional Exemplary Hydraulic Mechanism

FIG. 7H illustrates an additional embodiment of a hydraulic deliverysystem according to the invention. In the pictured embodiment, ahydraulic pump 3000 includes a smaller syringe 3002 within a largersyringe 3004. Smaller syringe 3002 is characterized by a first volume(V₁) volume and a first diameter (D₁), and larger syringe 3004 ischaracterized by a second volume (V₂) volume and a second diameter (D₂);where V₁<<V₂, and D₁<<D₂.

In one embodiment of the invention, each activation of an actuator 3006(e.g., handle rotation or foot pedal pressing) results in injection ofdefined amount of liquid from smaller syringe 3002 into reservoir 3010,optionally via flexible tube 3008. In an exemplary embodiment of theinvention, a uni-directional valve 3012, located at the distal end ofthe small syringe 3002, assures that liquid flows only towards reservoir3010. When activation of the actuator ceases, piston 3014 of the smallsyringe 3002 automatically returns to its original position. Theautomatic return of piston 3014 may be achieved, for example by use of aspring or an elastic band which applies force in a direction opposite toa direction of actuation. A second uni-directional valve 3016 is locatedin the wall between smaller syringe 3002 and larger syringe 3004. Whenpiston 3014 returns to its original position, a vacuum is created insidesyringe 3002. The vacuum and/or a force and/or a spring that pressespiston 3018 opens valve 3016 and liquid from larger syringe 3004 flowsinto the barrel of the small syringe 3002. According to this embodimentof the invention, liquid in larger syringe 3004 serves as a reservoirfor the refilling of the small syringe 3002. In an exemplary embodimentof the invention, a piston 3018 of larger syringe 3004 advances as V₂decreases. Optionally, this embodiment can provide force amplification(if D1 is greater than an ID of 3010; see detailed explanation below)and/or facilitates delivery of small and/or defined aliquots of liquidupon each activation of actuator 3006.

In many exemplary embodiments of the invention, the system is designedto assure that the hands of an operator is outside an X-ray radiationzone of an imaging or monitoring system employed in conjunction with thecement delivery system.

Pressure Amplification

Referring again to FIG. 7G, piston 2024 of pressure source 2004 ischaracterized by a first diameter (D1) and piston 2018 of cementreservoir 2002 is characterized by a second diameter D2.

If hydraulic fluid is present in 2026 and in 2028, the two chambersfunction as a single chamber and no hydraulic amplification is achievedeven if D1 and D2 are different.

In an exemplary embodiment of the invention, piston 2018 is pushed by adrive shaft (not shown) instead of by hydraulic fluid in 2028. Accordingto this exemplary embodiment, hydraulic amplification may be calculatedas follows:

The applied force (F) supplied by each piston can be calculated fromrelevant pressures (P) and diameters (D):F=P*A; whereA=π*D ²/4 thusF=P*π*D ²/4If pressure amplification is defined as pressure in cement reservoir2002 (P2) divided by pressure in pressure source 20042004 (P1), thepressure amplification is equal to (D1/D2)².

In an exemplary embodiment of the invention, pressure source 2002 is adesigned to be held in one hand, while a second hand operates handle2012. This design is compatible with an internal diameter D1 of 5 cm. Atypical cement reservoir has in internal diameter of 1.8 cm. Thisexemplary configuration produces a pressure amplification of 7.72.

For foot operated embodiments, D1 may be considerably larger (e.g. 10cm, 15 cm, 20 cm or intermediate or larger sizes) and a greater pressureamplification may be achieved.

Alternatively or additionally, mechanical amplification applies as inany manual device that uses a rotational drive with a lever arm (e.g.handle 2012 and cap 2013 in FIG. 7G or lever 4100 and gear 4140 in FIG.7V). These mechanical amplifiers further reduce the amount of inputforce required to achieve a large force to drive the piston in thecement reservoir (e.g. 2002 or 4005).

Unit Material Provision System

FIG. 8A shows a delivery system 800 in which material is provided asdiscrete units, each of which is of relatively small volume, forexample, 1/2, 1/4, 1/7, 1/0 or less of the amount required fortreatment. One potential advantage of working in units is that anoperator is more aware of the effect of his/her actions as each actioncan only inject one unit. Another potential advantage of working inunits is that units with different material properties may be providedduring a procedure. Another potential advantage is that units beingsmall will generally exhibit a smaller friction with the deliverysystem.

System 800 comprises a delivery tube 802 having one or more extrusionapertures 804 at its tip. A barrel 808 on which tube 802 is mounted,also includes an optional magazine 820, described below. A body 818 withan optional nut threading is optionally attached to barrel 808. A pusher810 lies within delivery tube 802 and/or barrel 808.

In an exemplary embodiment of the invention, a handle 812 is providedwhich includes a battery powered mechanism for advancing pusher 810. Ahydraulic mechanism such as described above may be used instead.Optionally, one or more switches are provided, for example, an on/offswitch 816 and a direction switch 814. Optionally, when pusher 810completes its forward motion, it is automatically retracted. Optionally,only a single switch is needed, activation of which causes extrusion ofone unit. In an exemplary embodiment of the invention, handle 812 isrotationally locked to body 818, for example using one or more guidepins.

In an exemplary embodiment of the invention, handle 812 comprises amotor and a battery that rotate pusher 810. An alternative mechanism isdescribed below.

Referring to magazine 820, in an exemplary embodiment of the invention,the magazine comprises discrete units 822 of material (a unit 824 isshown inside tube 802). Optionally, a spring 826 is used to push theunits towards tube 802. Optionally, the magazine is filled with acontiguous mass of material and the units are defined by the cuttingaction caused by pusher 810 pushing a unit of material away from themagazine.

In an exemplary embodiment of the invention, a magazine is preparedahead of time, for example, by a manufacturer, who fills the magazinewith a non-setting material.

In an exemplary embodiment of the invention, the magazine is loaded witha series of units of different properties, for example, responsive to anexpected progress of a procedure, for example, first providing a softmaterial and then providing a harder material, or vice versa.Alternatively, a rotating magazine is used, in which a user can selectwhich of several compartments will load barrel 808 next. This allowsfine control over the injected material. In an exemplary embodiment ofthe invention, an operator can remove magazine 820 at any time andreplace it with a different magazine. Optionally, this is done whilepusher 810 is forward, so that there is no danger of backflow from thebody.

Optionally, one or more of the units comprises or is an implant device(rather than an amorphous and/or homogenous mass), for example, anexpanding implant or an implant whose geometry does not change.Optionally, one or more of the units comprises a cross-linked material.

In an exemplary embodiment of the invention, the delivery system usedcomprises two or more delivery tubes (optionally the combined geometryhas a cross-section of a circle or of a figure eight). Optionally, eachtube has a separate pusher mechanism and/or a separate material source(e.g., a magazine). Optionally, the two tubes are used simultaneously.Optionally, an operator can selectively use one tube. Optionally, thematerials provided in each tube are components that react chemically onewith another. Optionally, electronic control is provided to control therelative provision rates of the two tubes. Optionally, this allowscontrol over the final material properties. Optionally, the use of twoor more tubes allows a layered structure to be built up in the body.Optionally, one of the tubes delivers a setting material and the othertube delivers a non-setting material. In an alternative embodiment, eachtube is used to provide a different component of a two componentmaterial. Optionally, the two tubes meet at their distal end, to ensuremixing of the components.

In an exemplary embodiment of the invention, the delivered material isCORTOSS by Orthovita inc. (US), a composite of Bis-GMA, Bis-EMA andTEGDMA. This material is optionally mixed along the path in the deliverytube.

In an exemplary embodiment of the invention, instead of the units beingprovided by a magazine or by a cutting mechanism, a partial unitbehavior is provided by the motor of handle 812 stopping after every“unit” advance. Optionally, mechanical stops are provided for ahydraulic mechanism, if used. Optionally, instead of stopping, a soundis provided when a unit is injected or based on a different logic, forexample, when 50% or another percentage of planned amount of material isprovided. Optionally, a CPU is provided which analyzes an image providedby an imaging system and generates a signal when a sufficient and/ornear sufficient and/or over-load amount of material is provided. Othercircuitry may be used as well.

Optionally, circuitry is provided for controlling the rate and/orpressure of material provision. Optionally, the circuitry stopsadvancing if a sudden change in resistance is perceived.

In an exemplary embodiment of the invention, the delivery systemincludes pre-heating or pre-cooling of the injected material and/or oftube 802. In an exemplary embodiment of the invention, a Peltier coolerand/or a resistance heater are provided in barrel 808. Other cooling orheating methods, such as based on chemical reactions or phase changingmaterials, may be used.

In an exemplary embodiment of the invention, the magazine is a longcoiled magazine. Alternatively or additionally, the deformable materialis folded in the magazine. Optionally, the magazine is elongated.Optionally, separate loading and pushing mechanism are provided. In anexemplary embodiment of the invention, for loading, a unit is insertedthrough a slot in the side of the barrel. For pushing, the unit isadvanced under a low pressure past the slot (or the slot is sealed) andonly then is significant pressure required to advance the unit, forexample, once the leading edge of the unit reaches the extrusionapertures.

FIG. 8B shows the implementation of a unit delivery method even withouta cassette. A delivery tip 840 of the cannula is shown with a lateralaperture 842 through which multiple units 822 are shown exiting.Optionally, an indication is provided to the user as a unit exits, forexample, based on motion of a pusher used. Optionally, the system ofFIG. 8A is used to load a series of units 822 into the barrel, forexample, pulling back the pusher after each unit is advanced past thecassette. In an exemplary embodiment of the invention, a distal tip ofthe cannula is closed, optionally permanently closed, so that cement 822is forced laterally outwards via aperture 842.

Battery Powered Pusher

FIGS. 9A and 9B show a material pusher 900 with reduced materialtwisting, in accordance with an exemplary embodiment of the invention.

As in the delivery systems described above, pusher 900 comprises adelivery tube 902 having one or more apertures 904 near its end.Optionally, an offset is provided between the apertures and the far tipof tube 902, for example, to ensure centering (or other positioning) ofthe extruded material, for example preventing the material from beingprovided too close to a far end of the vertebra, if the delivery systemis pushed forward.

Tube 902 is mounted (e.g., optionally replaceably) to a body 908. Apusher 910 is used to advance material through tube 902.

In an exemplary embodiment of the invention, in use, an operator pressesa switch 912, for example, to select between forward, backwards and nomotion of pusher 910. Power from a battery 914 (or a hydraulic or othersource) is conveyed to a motor 916. Rotation of the motor causes a nut922 to rotate relative to pusher 910. Optionally, a series of gears areused which may or may not provide a mechanical advantage, depending onthe implementation. In an exemplary embodiment of the invention, motor916 rotates a gear 918 that rotates a gear 920, which rotates nut 922which is coaxial thereto. Optionally, a rotation preventing element 924,for example, a rectangular element 924 is mounted on pusher 910 andprevents rotation thereof.

Optionally, one or more sensors are used to detect the extremes ofpositions of pusher 910, when it is advanced and when it is retracted.In the example shown, a micro-switch 926 and a micro-switch 928 detectthe ends of motion of pusher 910, for example, using a bump orelectrically conducting section 930 (depending on the sensor type used).Alternatively or additionally, a positional encoder is used, forexample, by counting rotation, or a separate encoder as known in the artof encoders.

FIG. 9B shows system 900 after extrusion is effected, showing extrusions932. Optionally, extrusions 932 are an extension to tube 902, prior tothem being cut off by pusher 910. In an exemplary embodiment of theinvention, rotation of tube 902 causes extrusions 932 to act as areamer. In an exemplary embodiment of the invention, the viscosity andshear strength of the material are selected to effect a desiredlimitation on the reaming abilities, for example, to prevent damage tobone.

Optionally, one or more gears are provided to rotate and/or oscillatethe delivery tube as the material is advanced. Optionally, periodic orramp axial motion is provided, by motor means. Optionally, the distaltip of the delivery tube is made soft, for example by attaching a softtip thereto, to reduce or prevent damage to the vertebra.

Sleeve Provision System

FIGS. 10A and 10B shows a sleeve based delivery system 1000, inaccordance with an exemplary embodiment of the invention. FIG. 10A is ageneral cut-open view of system 1000, in which a sleeve 1010 is notshown. FIG. 10B shows the distal portion of system 1000, includingsleeve 1010 mounted thereon.

The embodiment of FIGS. 10A-10B also illustrates a refilling mechanismby which the delivery tube includes a port to which a refill system canbe connected to refill the delivery tube with material to be injectedinto the body.

A pusher 1004 pushes material that is found inside a delivery tube 1002.In the embodiment shown, the material is ejected past a tip 1008 ofdelivery tube 1002. A sleeve 1010 is provided so that the sleeve liesbetween the material and delivery tube 1002. An optional tube cutter1012, such as a knife is shown to optionally split the tube after itexits the body. A pulley system 1011 for collecting the split tube isalso shown.

In operation, an amount of material is either provided in tube 1002 oris injected into it, for example, via a port 1016 in pusher 1004.Advancing of pusher 1004, for example, by applying force to a knob 1018attached thereto, for example manually, using a motor or using othermechanisms described herein, pushes against the material in tube 1002.At the same time, sleeve 1010, which is attached to pusher 1004, forexample, by a crimping 1014, is pulled along with the material. Portionsof sleeve 1010 reaching distal tip 1008 of tube 1002, fold back towardsa body 1006 of delivery system 1000. When sleeve 1010 reaches knife1012, it is optionally split so that it can pass over tube 1002 andpusher 1004. A thread or wire or other coupling 1013 is attached to theproximal (split) side of sleeve 1010 (e.g., via a connector 1019) andvia a pulley 1011 is pulled as pusher 1004 advances. A slide 1020 isoptionally provided to guide the motion of the split sleeve

It should be appreciated that such a sleeve system can also be used fordelivering implants rather than material. In one example, a compressedplastic implant, for example, polyurethane, which is compressed radially(and extended axially) is advanced using a sleeve system, to reducefriction. Optionally, the sleeve material is selected according to thematerial being used and/or the tube material. In another example, thesleeve system is used to deliver a self-expanding implant, for example,as described in WO 00/44319 or in WO 2004/110300, the disclosures ofwhich are incorporated herein by reference.

It is noted that a sleeve system may also be flexible. Optionally, thesleeve is formed of a chain-link or a knitted material, rather than anextruded plastic polymer tube. Optionally, the sleeve is formed ofmultiple layers of materials, for example by extrusion or by lamination.Optionally, fibers or other strengthening means are provided to reduceelongation. Optionally, the sleeve is formed of a material thatwithstands heat and/or chemical byproducts caused by PMMA. Optionally,the sleeve is preformed to elastically expand when it exits the deliverytube. Optionally, the sleeve is perforated or includes a plurality ofapertures therein.

Optionally, the sleeve elutes one or more treatment materials.Optionally, the sleeve elutes one or more catalysts or catalysisretarding materials, for example, to prevent or slow-down reactions inthe delivery system and/or speed them up out of the delivery system.

Optionally, a layer of oil or other lubricant is provided in addition toor instead of the sleeve.

Optionally, the sleeve remains inside the body, for example, beingformed of a bio-degrading materials or maintaining its form. Optionally,when degrading, strengthening fibers or other elements remain to enhancethe strength of the extruded material or implant.

FIG. 10C is a cross-sectional view of a variant system 1000′ in which apusher 1004′ is flexible enough to bend. This allows a body 1006′ of thedevice to be manufactured in a non-linear shape, for example, in theshape of revolver, which may be easier to hold. Optionally, one or morewheels, bearings or slides (not shown) are used to guide pusher 1004′.Optionally, pusher 1004′ can be made more flexible as some of the motiveforce used to move the material is provided by the sleeve pulling thematerial forward. Alternatively or additionally, some reduction issupported by the reduced friction.

Optionally, a sleeve system is used with a magazine system, for example,the units being provided through port 1016.

Optionally, the sleeve is pre-split and includes an overlap to preventfriction in the delivery tube. Optionally, this allows a magazine toload the sleeve from the side.

FIG. 10D shows a further, compact, variant 1000″ in which a pusher 1004″is made flexible enough to fold over itself, so body 1006″ can be ofsmaller dimensions. It should be noted that these more compact and/ornon-linear embodiments can also be practiced without the sleeve feature.The sleeve pullback mechanism is not shown here.

FIG. 10E shows a variant system 1000′″ in which a pusher 1004′″ isreduced in size axially. In this design the motive force is provided bypulling back the cut sleeve 1010 using a knob 1040 (or a motorized ormechanical gain or other means). This pulling back advances a shortenedpusher 1004′″. Optionally, pusher 1004′″ is provided as a sealed end ofsleeve 1010. A body 1006′″ of the system can be very compact, dependingon the method of pulling back on knob 1040. Op two or more symmetricallypositioned knifes 1012 are provided, to allow for proper mechanicalsupport of tube 1002 by body 1006′″. Optionally, the tube is precut.

In an exemplary embodiment of the invention, it is noted that pusher1004 is separated from the injected material by the sleeve. Optionally,a hydraulic system is used to advance the pusher, for example (in FIG.10F) attaching a flexible tube to pusher 1004′″ in tube 1002.

In an exemplary embodiment of the invention, sleeve 1010 is used toisolate the body itself from the hydraulic system, possibly allowing fora system with a higher probability of leaking.

In the embodiments shown, the material exited from the distal end 1008of tube 1002. Optionally, a stop is provided at the end, so that thematerial is forced sideways. Optionally, the stop is not attached totube 1002 at end 1008 thereof. Rather a thread, running through tube1002 and/or outside thereof (or more than one thread) attaches the stopto the body of device 1000. Optionally, the thread runs through a narrowlumen formed in pusher 1004.

Alternatively, one or more elements which attach the stop to tube 1002,serve to split sleeve 1010, at tip 1008 of tube 1002. In an exemplaryembodiment of the invention, the stop is attached to tube 1002 after thesleeve is mounted thereon. Alternatively, the sleeve is pre-split,pulled through tube 1002, past the elements and attached to connector1019.

In an alternative embodiment of the invention, the sleeve is providedtotally within the delivery tube. In one embodiment (not shown), thedelivery tube comprises two coaxial tubes and the inner tube serves asshown by tube 1002 in FIGS. 10A-10E.

In another embodiment, the fact that the delivery tube is full ofmaterial is taken advantage of, in that the material (316) serves toprevent the tube from collapsing when it is simultaneously pushed fromone end and pulled from the other. This may depend on the viscosity ofthe material and/or on the shape of the distal tip of the deliverysystem. Optionally, the distal end is slightly flared to define afolding over location for the sleeve.

FIG. 10F shows such an embodiment, of a delivery system 1050, in whichsleeve 1010 is provided within delivery tube 1002. As can be seen afolding over location 1052 for the sleeve is provided past the end oftube 1002. In an exemplary embodiment of the invention, a ring (notshown) is provided past the end of tube 1002 and around which the sleeveis folded. This ring serves as a scaffold for the folding, but due toits having a diameter greater than an inner diameter of tube 1002 (or atleast being misaligned if the ring and/or tube are not circular incross-section), cannot be pulled into the tube by retraction of sleeve1010.

In an alternative embodiment of the invention, sleeve 1010 does not foldback towards system 1000. Rather, the sleeve is pushed into the vertebrawith the material. Optionally, once out of the confines of tube 1002,the material can tear the tube. In an alternative embodiment, the sleeveremains intact and encloses the material, sausage-like, in the body. Thesleeve may be formed of biocompatible, bioabsorbable and/or implantgrade material.

Squeeze Based Material Provision

In an exemplary embodiment of the invention, the material is squeezedout of the delivery system rather than pushed. FIG. 11A shows a squeezebased system 1100, in which a delivery tube 1102 is made out of asqueezable material, such as a polymer or annealed metal. A pair ofrollers 1104 (or one roller and an opposing anvil, not shown) advancetowards the distal side of tube 1102, squeezing it flat and forcingmaterial that fills the tube to migrate distally. Various motionmechanism can be used. In the figure, the motion mechanism is a lineargear 1108 which engages a gear 1106 that is coaxial with roller 1104.When the roller is rotated, the linear gear advances the roller. Variouspower sources may be used, for example, electric motors and hydraulicpower. Also, other power trains may be used. The rollers are optionallymade of stainless steel.

FIG. 11B shows a delivery system 1120, in which a squeeze element 1124slides rather than rolls against a delivery tube 1122. Tube 1122 isoptionally rolled around a pin 1134. Various mechanisms can be used tomove squeeze element 1124, for example a motor 1130 attached to a cable1126 via an optional pulley 1128.

Tamping Method

In an exemplary embodiment of the invention, friction is reduced byreducing the length of motion of the material inside a delivery tube. Inone method, a small amount of material is provided into a distal side ofa delivery tube (while outside the body). Then the distal part isinserted into the body and a tamping tool is provided into the proximalpart.

This process may be repeated several times until a desired amount ofmaterial is provided into the body.

Penetrating Delivery System

In some embodiment of the invention, the delivery system also penetratesto the bone and/or penetrates the bone. Optionally, this obviates theneed for a separate cannula and/or may simplify the procedure.Optionally, the delivery tube is kept in the body when it is beingrefilled with material to be injected.

FIG. 12A shows a penetrating delivery system 1200. A distal tip 1202 isformed in a manner suitable for drilling in bone. This is shown ingreater detail in FIG. 12B which illustrates one exemplary embodiment ofa bone cement cannula with a lateral ejection aperture 1204 and apermanently closed distal tip 1202.

A hydraulic pump or mechanical ratchet advance mechanism is optionallyused, with a handle 1206 used for pumping shown.

A potential advantage of a one piece system is that fewer parts areneeded. If the system is preloaded with all the material needed, forexample, at a manufacture, no equipment changes are needed. Optionally,the use of a side aperture 1204 allows the tip to be a drilling tip.Optionally, the use of smaller diameter tubes allows fewer parts to beused, as drilling is simplified.

Optionally, the proximal end of system 1200 is adapted for tapping witha mallet.

FIG. 12C shows an alternative embodiment of a system, 1230, in which thesystem is adapted to ride on a guidewire 1236, for example, a K-wire. Inan exemplary embodiment of the invention, a bore 1238 is formed in adrilling section 1232 of system 1230. Alternatively, the bore is to theside of the drilling head, for example, exiting through an aperture 1234which may also be used for extruding material. Optionally, the pusher(not shown) is drilled as well. Optionally, the diameters of the drilledholes are too small for the material to exit through. Alternatively,bore 1238 is used for extruding material, after the K-wire is removed.

In an exemplary embodiment of the invention, the material is predrilledwith a bore, to allow passage of the guidewire therethrough. Optionally,this bore is provided with a sleeve. It is noted that absent axialpressure on the material, the material will generally not flow into thedrilled bore. Alternatively or additionally, the guidewire is coatedwith a suitable friction reducing coating, solid or fluid.

Optionally, the delivery tube is loaded after the delivery tube isguided into the body (and the guidewire removed), for example using abarrel storage means or a unit magazine as described above.

Optionally, a separate lumen is defined for a K-wire. Optionally, thatlumen is a collapsible lumen. However, until pressure is applied to thematerial to be delivered, it remains un-collapsed. Once the guidewirecompleted its task, it is removed and pressure applied to the material,collapsing the guidewire channel and improving the flow characteristics(by increasing effective inner diameter of the delivery tube.

In an exemplary embodiment of the invention, a cannula is not needed,for example, if the delivery system rides on the guidewire or if thedelivery system is used to directly penetrate the bone. Optionally, thedelivery tube of the delivery system is not removed once inserted intoor to the bone, for example, using a barrel or pumping mechanism asdescribed above to reload the delivery mechanism if required. Once thesystem is reloaded, the pusher can advance the material into thedelivery tube where it can then be advanced into the bone.

Mixing Apparatus

FIGS. 14A-14B illustrate an exemplary high shearing force mixingapparatus 4000 adapted for mixing a viscous mixture according to anexemplary embodiment of the invention.

FIG. 14A is an exploded view of apparatus 4000 and FIG. 14B is aperspective view of the same apparatus after assembly. In an exemplaryembodiment of the invention, apparatus 4000 is used for mixing thecomponents of high viscosity bone cement.

In an exemplary embodiment of the invention, mixing apparatus 4000comprises a container 4002, a mixing paddle 4004, a revolving plate4005, gears 4006, axles 4008 and 4009, a cover 4010, and a handle 4012.In an exemplary embodiment of the invention, mixing element 4004 has alarge surface area of 400, optionally 600, optionally 800, optionally1000 mm² or intermediate or greater values. Optionally, mixing paddle4004 is slotted or has holes distributed on its surface. Optionally,during operation mixing implement 4004 applies large shearing forces toa viscous mixture in well 4020. Optionally the large shearing forceassures complete mixing of a liquid phase and a solid phase (e.g. powderor beads).

In an exemplary embodiment of the invention, paddle 4004 is “wiped” onwalls of container 4020. Optionally, shearing forces and stresses mayvary with velocity of the revolving and/or paddle surface area and/orcement volume and/or cement viscosity.

In an exemplary use scenario of mixer 4000, the cement components areinserted into a mixing well 4020 of container 4002. The cementcomponents will typically initially include a solid phase (e.g. polymerbeads or powder) and a liquid phase.

In an exemplary embodiment of the invention, closing cover 4010 bylowering it onto container 4002 so that tabs 4025 are engaged by slots4030 prevents rotation of cover 4010 with respect to container 4002.Optionally, other rotational locking means are employed.

Revolution of handle 4012 turns axle 4008 and causes revolution of gears4006A, 4006B and 4006C. In an exemplary embodiment of the invention,axle 4008 is rotated by an electric motor, optionally a battery poweredmotor.

Mixing element 4004 is attached via its axle 4003 to gear 4006A locatedon revolving plate 4005. When axle 4008 is turned, it causes revolutionof gears 4006A, 4006B and 4006C.

Revolution of revolving plate 4005 causes axle 4003 of mixing element4005 to revolve about a center of mixing well 4020. The revolutionwithout rotation of mixing paddle 4004 causes the mixing element topress the mixture against each of the four wells of mixing well 4020 inturn. In an exemplary embodiment of the invention, this mixing patternreduces an amount of un-mixed material on inner walls of well 4020.

FIGS. 14C, 14D, 14E, and 14F are top views of mixing well 4020. Thedescribed sequential views of paddle 4004 describe how the apparatussuccessively presses material against walls of the mixing well. In anexemplary embodiment of the invention, axle 4003 moves along round path4016. Gears 4006A; 4006B and 4006C assure that paddle 4004 does notrotate around axis 4003. Thus, each of the four sides of the paddle 4004always faces the same direction (relative to walls of mixing well 4020).In an exemplary embodiment of the invention, paddle 4004 revolveswithout rotation because gears 4006A and 4006C each have the same numberof teeth. Gear 4006B is interposed between gears 4006A and 4006C tocause them to turn in a same direction. Optionally, gear 4006B has anydesired number of teeth.

As illustrated in FIG. 14C, as the paddle 4004 moves from the bottomwall towards the left wall, it applies pressure to a portion of themixture located near the left wall presses it against the left wall ofmixing well 4020 (FIG. 14D). The material being mixed tends to escapetowards the upper and lower walls of well 4020. As paddle 4004 continuesalong its path (FIGS. 14E) it contacts the upper wall of well 4020 andthen presses the mixture against the right wall (FIG. 14F) of well 4020.This mixing pattern provides constant flow of the material being mixedand homogeneous mixing of the mixture components, even at highviscosity.

Mixing apparatus 4000 may be constructed of a wide variety of materials.A choice of construction materials optionally considers the particulartype of bone cement to be mixed, its chemical characteristics and/orviscosity. In an exemplary embodiment of the invention, mixing well 4020and/or container 4002 are constructed at least partially ofpolypropylene and/or nylon. In an exemplary embodiment of the invention,paddle 4004 and/or axle 4003 are constructed of stainless steel. Gears4006A, 4006B and 400C are optionally constructed of plastic and/ormetal.

Once mixing is complete, cover 4010 can be opened and the mixed contentscan be removed from mixing well 4020.

Transfer of Viscous Material

In an exemplary embodiment of the invention, mixed viscous bone cementis removed from mixing well 4020 and transferred to a reservoir of adelivery system. Optionally, the reservoir is a cement reservoir asdescribed hereinabove. Optionally, the mixing well serves as a cementreservoir.

In an exemplary embodiment of the invention, viscous bone cement ismanually manipulated into a delivery system reservoir. Optionally,manual transfer includes shaping. In an exemplary embodiment of theinvention, viscous bone cement is manually shaped so that it roughlyconforms to a configuration of a delivery reservoir. For example, theviscous material may be rolled into a roughly cylindrical form with adiameter slightly smaller than a delivery reservoir into which thematerial is to be introduced. In an exemplary embodiment of theinvention, manual transfer includes use of a tool. For example, viscousbone cement is packed into a delivery reservoir using a tool.Optionally, the tool is a rod.

In an exemplary embodiment of the invention, viscous bone cement istransferred to a delivery reservoir via an aperture in mixing well 4020.Optionally, the aperture is a lateral aperture in a wall of well 4020.Optionally, the same aperture is used to introduce cement into well4020. In an exemplary embodiment of the invention, the aperture includesa connector connectable to the delivery system reservoir. Optionally,the connector connects the mixing apparatus to the delivery systemreservoir while the mixing apparatus operates.Transfer Apparatus

FIGS. 18, 19, 20 and 21 illustrate an exemplary embodiment of a transferapparatus 5000 for loading a viscous material into a container. In anexemplary embodiment of the invention, the container is a cementreservoir and the material is a viscous bone cement.

FIG. 18 illustrates cement reservoir 2003 assembled into a transferpiston 5020 to form a transfer assembly 5025.

FIG. 19 illustrates that assembly of cement reservoir 2003 and transferpiston 5020 is optionally by means of matched threads 5021 and 5022.

FIG. 21 illustrates assembly of transfer assembly 5025 into a container5011 of a mixing apparatus. Not pictured is the viscous material(optionally bone cement) in container 5011.

Transfer assembly 5025 is seated in container 5011 so that reservoir2003 faces outwards. Cover 5030 is optionally applied to container 5011,for example using threads 5031 so that reservoir 2003 protrudes fromhole 5032 as seen more clearly in FIG. 20.

Application of pressure to reservoir 2003 and/or an upper edge of piston5020 causes piston 5020 to descend into container 5011. In an exemplaryembodiment of the invention, cover 5030 applies pressure to upper edgeof piston 5020 o as it is attached to container 5011. Cement incontainer 5011 is displaced upwards into reservoir 2003. When thereservoir is sufficiently filled, it is removed from piston 5020. In anexemplary embodiment of the invention, the reservoir is transferred to adelivery system as described hereinabove.

FIGS. 22; 23; 24; 25 and 26 illustrate an exemplary embodiment of theinvention in which container 5011 is a mixing well of a mixer 4000.

FIG. 22 is a cross sectional view of the mixer containing cement 4021.Cover 4010 is held in place by mated threads 4011 and 4012.

FIG. 23 is a cross sectional view of the mixer containing cement 4021with cover 4010 removed. Mixing well 5011 becomes the basis for transferapparatus 5000.

FIGS. 24 and 25 are cross sectional views illustrating assembly ofcement reservoir 2003 into transfer piston 5020. Optionally, assembly isvia mated threads 5022 of reservoir 2003 and 5021 of transfer piston5020. Cover 5030 is optionally employed to force transfer piston 5020downwards into mixing well 5011. Cover 5030 may be threaded onto mixingwell 5011 via complementary threads 5031 and 4011. In an exemplaryembodiment of the invention, cover 5030 is screwed onto well 5011 toforce piston 5020 downwards onto cement 4021.

FIG. 25 illustrates that downward motion of piston 5020 forces cement4021 to rise upwards into reservoir 2003 towards aperture 2500.

FIG. 26 illustrates removal of reservoir 2003 filled with cement 4022 bydisengagement of threads 5022 from matching threads 5021. Optionally, afloor of mixing well 5011 and/or a base of transfer piston 5020 are notstraight. In an exemplary embodiment of the invention, this reduces anamount of residual cement in well 5011 after transfer.

Optional Additional Therapy

In an exemplary embodiment of the invention, the provision of materialis enhanced by additional therapy. Optionally, the additional therapycomprises thermal therapy. Optionally, the material is pre-heated orpre-cooled. Optionally, the pre-heating or pre-cooling also serves apurpose of controlling the material properties and/or setting behavior.

In an exemplary embodiment of the invention, the heating is by contactheat (conduction) or by radiofrequency energy or light, for example aflash lamp or a laser source. Alternatively or additionally, thedelivery system radiates heat. Optionally, a microwave or other wirelessheating method is used.

Optionally, heating is provided separately from material provision. Inone example, a heated guidewire is provided into the vertebra.Optionally, the guidewire extends one or more protrusions, to guidethermal energy into the nearby tissue. Optionally, a thermal sensor isprovided to control the temperature in the vertebra and/or prevent overheating.

In an exemplary embodiment of the invention, temperature control isapplied to increase the handling and/or working time of the bone cement.Optionally, a temperature control unit operates on cement in an externalreservoir and/or cement in a delivery system reservoir. In an exemplaryembodiment of the invention, the temperature control unit includes aresistive coil powered by an electric power source, optionally abattery.

Exemplary Materials

Various materials are suitable for use with exemplary embodiments of theinvention. Some of the materials which can be used in some embodimentsof the invention are known materials, for example, PMMA, however, theymay be used at unusual conditions, for example at a semi-hardenedcondition. Also, while putty materials may be known, they are nottypically used for injection through a small bore into bone.

It should be noted that while specific examples are described it isoften the case that the material composition will be varied to achieveparticular desired mechanical properties. For example, differentdiagnoses may suggest different material viscosities.

In an exemplary embodiment of the invention, for non-hardeningmaterials, the material can be allowed to set outside the body. Aftersuch setting the material may be washed or ventilated. In this manner,some materials with potentially hazardous by-products can be safelymixed and then used in the body. Optionally, a material is tested tomake sure toxic byproducts are removed to below a safety threshold.Optionally, a testing kit is provided with the delivery system.

In an exemplary embodiment of the invention, the material is selected sothat its mechanical properties match the bone in which it will beimplanted. In an exemplary embodiment of the invention, the material ismatched to healthy or to osteoporotic trabecular bone. Optionally, themechanical properties of the bone are measured during access, forexample, based on a resistance to advance or using sensors providedthrough the cannula or by taking samples, or based on x-raydensitometers measurements.

In general, PMMA is stronger and has a higher modulus than trabecularbone. For example, Trabecular bone can have a strength of between 3-20megapascal and a Young modulus of 100-500 megapascal. Cortical bone, forexample, has strength values of 170-190 gigapascal and Young modulus of13-40 gigapascal. PMMA typically has values about half of Cortical bone.

In an exemplary embodiment of the invention, the material is selected tobe less than 120% as strong and/or young modulus as the expected bone tobe treated. Optionally, the values of one or both of strength and youngmodulus are 10%, 20%, 30%, 40% or less reduced from that of trabecularbone. It should be noted that if less of the vertebra is filled, theinjected material will be supported, at least in part, by trabecularrather than cortical bone, depending for example on the method of filingof interior 308.

Exemplary Non-hardening Material

In an exemplary embodiment of the invention, the material used is aputty like material. One example of a putty-like material is ahydroxyapatite with an increased ratio of sodium alginate. For example,the increased ratio can be 8% or 10%. While this material does harden inthe body, it does not set to a hardened condition absent humidity. Thusit can be prepared ahead of time and pre-stored in a delivery system,for example by a manufacturer. In an exemplary embodiment of theinvention, the added material slows down water absorption so that whilesufficient water enters the material to initiate setting, not enoughenters to cause dissolution. An example of this material is described inIshikawa et al., “Non-decay fast setting Calcium phosphate cement:Hydroxyapatite putty containing an increased amount of sodium alginate”,J Biomed Mater Res 36 1997, 393-399, the disclosure of which isincorporated herein by reference. More details may be found in “Effectsof neutral sodium hydrogen phosphate on setting reaction and mechanicalstrength of hydroxyapatite putty”, by Kunio Ishikawa, Youji Miyamoto,Masaaki Takechi, Yoshiya Ueyama, Kazuomi Suzuki, Masaru Nagayama andTomohiro Matsumura, in J Biomed Mater Res, 44, 322-329, 1999, thedisclosure of which is incorporated herein by reference.

Other calcium derivative cements, bone chips and/or fillers may be usedas well. Bone chips, depending on processing may have a limited shelflife. Some of these materials generally harden (or combine with bonegrowth) after a relatively long time, such as more than a week, morethan a month or more than 3 months.

Additional Exemplary Non-hardening Material

In an exemplary embodiment of the invention, the material used is amixture of LMA (lauryl methacrylate) and MMA (methyl methacrylate).Depending on the ratio used, different mechanical properties andviscosities can be achieved. FIG. 13 is a graph showing the relativeviscosities of PMMA and various ratios of the copolymer material. In theexample shown, as the ratio of LCA decreases, viscosity goes down.

Diblock copolymers of MMA and LMA were synthesized by anionicpolymerization using DPHLi as initiator in THF at −40° C. with thesequential addition of monomers. The molecular weight distribution ofthe polymers was narrow and without homopolymer contamination when LMAwas added to living PMMA chain ends.

In an exemplary embodiment of the invention, the ratio used are 80:20,70:30, 60:40, 50:50, 30:70, 20:80 or intermediate, smaller or largerratios (by volume).

EXPERIMENT Materials and Methods

Starting Materials

Medicinal distillate methyl methacrylate and lauryl methacrylatestabilized with 10-100 ppm of the monomethyl ether of hydroquinone wereused as received from Fluka, Germany. Benzoyl peroxide (BPO) waspurchased from BDH Chemicals, England. N Barium sulfate (BS) wasobtained from Sigma-Aldrich (Israel). All solvents were analytical-gradefrom Biolab (Jerusalem, Israel) and were used as received.

Polymerization

Polymerization reactions were carried out in a single necked roundbottom flask equipped with a magnetic stirring. In a typical reaction,60 ml MMA (0.565 mol), 50 ml LMA (0.137 mol), 220 mg of Benzoyl Peroxide(0.9 mmol), and 100 ml THF were transferred. The amount of BPO wasadjusted to each of the compositions according to the total amount ofthe monomer's mols. The amount of the THF was equal to the total volumeof the monomers (table 1). The content was heated to a polymerizationtemperature of 70-75° C. for 20 hours, then the solution wasprecipitated in sufficient amount of methanol and left to mix for fourhours. Finally, the polymer was dried in an oven at 110° C. undervacuum.

TABLE 1 copolymers composition Copolymer MA LMA BPO THF (MA:LMA)(ml/mol) (ml/mol) (mg/mol) (ml) 100:0  100(0.94)  0(0)  285(1.18) 10080:20 80(0.75) 20(0.07) 258(1.06) 100 70:30 70(0.66) 30(0.10) 239(0.99)100 60:40 60(0.56) 40(0.14) 220(0.9)  100 50:50 50(0.47) 50(0.17)201(0.83) 100 40:60 40(0.38) 60(0.20) 182(0.75) 100 30:70 30(0.28)70(0.24) 163(0.67) 100 20:80 20(0.19) 80(0.27) 144(0.6)  100  0:1000(0)  100(0.34)  107(0.44) 100

The dried polymer was milled to a fine powder (Hsiangtai Sample mill,model sm-1, Taiwan) and mixed with barium sulfate (30% w/w). The mixturewas heated in a glass inside a sand bath to 140° C., until melting ofthe polymer. The mixture left to cool, and milled again. This procedurewas repeated at least three times, until a homogeneous off-white polymerwas received, which could be melted into loadable slugs for the deliverysystems and magazines described above.

Characterization

Molecular weight and polydispersity were analyzed by Gel permeationchromatography, GPC system consisting of a Waters 1515 isocratic HPLCpump with a Waters 2410 refractive-index detector and a Rheodyne(Coatati, Calif.) injection valve with a 20-1 μL loop (Waters Ma). Thesamples were eluted with CHCl₃ through a linear Ultrastyragel column(Waters; 500-Å pore size) at a flow rate of 1 mL/min.

¹H-NMR spectra were recorded on a Varian 300 MHz instrument using CDCl₃,as solvents. Values were recorded as ppm relative to internal standard(TMS).

A Cannon 1C A718 Ubbelhold viscometer was used for the viscositymeasurements of the polymer. The measurements were performed at 30° C.with toluene as a solvent.

Water Absorption Capacity.

Swelling behavior of acrylic bone cements was carried out fromaccurately weighed films of 0.8 mm thickness. Films were introduced in0.9 wt % NaCl solution (20 ml) and kept at 37° C. The water sorptionkinetics in 20 ml saline solution were evaluated in two specimens ofeach bone cement (containing 30% barium sulphate).

Equilibrium gain was determined gravimetrically at different periods oftime. The uptake of water was recorded at 30 min intervals in thebeginning and spacing out these intervals until the equilibrium wasattained. At appropriate times, the samples were removed, blotted withabsorbent paper to remove the water attached on its surface and weighed.The percentage of Equilibrium gain was obtained from each specimen usingthe following expression:

${{Hydration}\mspace{14mu}{degree}\mspace{14mu}(\%)} = {\frac{{{Weight}\mspace{14mu}{of}\mspace{14mu}{swollen}\mspace{14mu}{specimen}} - {{initial}\mspace{14mu}{weight}\mspace{14mu}{of}\mspace{14mu}{specimen}}}{{initial}\mspace{14mu}{weight}\mspace{14mu}{of}\mspace{14mu}{specimen}} \times 100}$Results:

100% PMMA: Average 1.845% (+0.045)

-   -   Initial weight (g) 0.2156 and 0.2211    -   Weight of specimen at equilibrium (g) 0.2195 and 0.2253    -   Equilibrium gain (%): 1.8 and 1.89;

60% PMMA, 40% PLMA: Average 1.65% (+0.235)

-   -   Initial weight (g): 0.1161 and 0.1402    -   Weight of specimen at equilibrium (g) 0.1183 and 0.1422    -   Equilibrium gain (%): 1.42 and 1.89;

50% PMMA, 50% PLMA: Average: 1.02% (+0.28)

-   -   Initial weight (g): 2700 and 0.2371    -   Weight of specimen at equilibrium (g) 0.2720 and 0.2400    -   Equilibrium gain (%): 0.74 and 1.3;        Compression Testing

These tests were conducted using an Instron 4301 universal testingmachine provided with a load cell of 5 kN, and at a cross-head speed of20 mm/min. A known weight of polymer was melted in a glass inside a sandbath. The bath was heated at 150° C. for two hours, and then bariumsulfate was added (30% w/w) and mixed well several times, untilhomogenous dough was received. Cylindrical specimens of 6 mm in diameterand 12 mm high were prepared by forcing the melted copolymers into theholes of a Teflon mold. One side of the mold was covered with Teflonplates and secured with clamps. The specimens were cooled for 20 minutesin the mold, then the upper side was cut to the mold shape, and thespecimens removed from the mold, finished to a perfect cylindricalshape. The test took place at least 1 week after aging in air at 23±1°C. For each cement composition, six specimens were tested. The elasticmodulus and the maximal strength force were obtained.

Results:

Molecular Weights and Viscosity Measurement

The number and weight average molecular weights of poly (La-MA), poly(MMA) and their copolymers were obtained from gel permeationchromatography. The polydispersity index varies in the range of 1.6 to2.87. The viscosities of the polymers are obtained using Toluene assolvent at 25° C. The intrinsic viscosities (η) were obtained byextrapolating η_(sp C) ⁻¹ to zero concentration. The molecular weightsand viscosities are presented in Table II.

TABLE II composition Feed Ratio GPC analysis of polymers MMA:LMA NMRAnalysis Poly- Vol.-% (mol-%) [MMA]:[LMA] M_(n) M_(w) dispersity [η]100:0 (100:0)  100:0  65190 119544 1.833 0.544  8:2 (91.5:8.5) [88]:[12]69118 119194 1.724 0.421 7:3 (87:13) 87:13 63006 112442 1.78 0.393 6:4(84:16) 84:16 73295 118384 1.615 0.366 1:1 (74:26) 69:31 94167 1358801.44 0.351 4:5 (69:31) 70:30 55455 104711 1.888 0.316 4:6 (64:36) 62:3875648 134745 1.781 0.305 3:7 (56:44) 56:44 35103 79986 2.27 0.221 2:8(40:60) 40:60 23876 68720 2.87 0.178 0:100 (0:100)   0:100 27350 751462.74 0.083Compressive Test.

The results of the compressive test are collected in Table III as afunction of compressive strength and modulus. The influence on themechanical behavior of adding lauryl methacrylate monomers can beclearly observed. The introduction of higher percentages produces adecrease that is more pronounced at 50% (v/v) LA. The compressivemodulus shows a drastic decrease as the content of LA increases. Thisdrop may be related to the structure modification of the matrix by theintroduction of LMA. This drop may also limit the use of somecompositions for some applications.

TABLE III compression test results Composition Max strength ModulusMA:LA (V %) (Mpa) (Mpa) 1:0 106.8(9)    2478(220)  8:2 82.5(17.1)1100.7(129)   7:3 63.3(13.2) 634.5(116)  6:4 48(11) 550(250) 5:518.9(4.5)  69.6(20)  4:6 1.9(0.2) 49.5(11.8) 3:7 19.19(3.42)  8.3(1.2)2:8 0.253(0.06)   1.71(0.417)Material Modifications

Optionally, various additives are added to the materials describedherein, to modify their properties. The adding can be before setting orafter setting, depending on the material. Exemplary materials that canbe added include fibers (e.g., carbon nanotubes or glass fibers) ofvarious lengths and thicknesses, aggregates and/or air bubbles.

In an exemplary embodiment of the invention, if the material ismanufactured to be anisotropic, it can be advanced into the body in adesired direction, for example, by selecting a delivery path (e.g.,storage, tube, aperture) to reduce twisting and/or deformation.Optionally, such materials are provided as short units (FIG. 8).

Softening and Semi-hardening Materials

In an exemplary embodiment of the invention, the material used softensafter provision into the body. In an exemplary embodiment of theinvention, the material comprises an additive that disperses or weaknessin water or body fluids, for example, salt. A softening material may beuseful if the forces required for height restoration are smaller thanthe forces required for maintaining height. Softening times areoptionally controlled by mixing in a gel material which slows down waterpenetration into the extruded material.

Semi-hardening Materials

In an exemplary embodiment of the invention, the material used sets tonon-hardened condition. In an exemplary embodiment of the invention, thematerial comprises MMA, LMA and NMP. NMP solvates in water, allowing thematerial to set somewhat. In an exemplary embodiment of the invention, ahardened condition is avoided, possibly preventing the induction offractures in nearby vertebra.

Use of Hardening Materials

In an exemplary embodiment of the invention, the above described devices(e.g., delivery) are used with a material which sets to a hardenedcondition, for example, PMMA or other bone cements and fillers. In anexemplary embodiment of the invention, the material is provided in a kitthat includes a timer and/or a viscometer, so that an operator canestimate the workability and viscosity of the material and itsusefulness for height restoration without leakage. Optionally, the timeincludes a temperature sensor and provides an estimate of workabilitytime based on the temperature and the time the components of the PMMAwere mixed.

In an exemplary embodiment of the invention, the cement includes anacrylic polymer, such as polymethylmethacrylate (PMMA). Optionally, thepolymer is supplied as beads. Optionally, styrene may be added. In anexemplary embodiment of the invention, a monomer (e.g.methylmethacrylate; MMA) is mixed with the polymer beads.

In general bone cements polymerize by radical-initiated additionreactions. In an exemplary embodiment of the invention, the cement isprepared from two separate components: a powder component containingprepolymerized beads (e.g. of PMMA or a PMMA/styrene copolymer) and aliquid component containing monomers (e.g. MMA).

In an exemplary embodiment of the invention, an intiator (e.g. benzoylperoxide (BPO) is incorporated into the powder and a chemical activator(e.g. DMPT) is incorporated into the liquid. Optionally, an easilyoxidized molecule (e.g. hydroquinone) is added to the liquid componentto prevent spontaneous polymerization during storage.

Optionally, cement may be rendered radiopaque, for example by adding aradio-opaque material such as adding barium sulfate and/or zirconiumcompounds to the powder and/or liquid component.

Optionally, the average molecular weight of PMMA in all beads is 80,000,optionally 100,000, optionally 120,000, optionally 140,000, optionally160,000, optionally 180,000 Dalton or intermediate or lesser or greatervalues. In an exemplary embodiment of the invention, the averagemolecular weight PMMA in all beads is approximately 110,000 Dalton.Optionally, at least some of the beads include styrene. In an exemplaryembodiment of the invention, styrene is added to PMMA beads in avolumetric ratio of 5-25%.

In an exemplary embodiment of the invention, at least some beads containpolymer (e,g. PMMA and/or styrene) with a higher molecular weight,Optionally, the higher molecular weight is 600,000, optionally 900,000,optionally 1,100,000 Dalton or intermediate or lesser or greater values.Optionally, polymer beads (e,g. PMMA and/or styrene) with the highermolecular weight comprise 0.25%, 0.5%, 1%, 2%, 3%, 4%, 5% orintermediate or lesser or higher of the total bead population. In anexemplary embodiment of the invention, this type of formulation providesa cement characterized by a short mixing time and/or a cement whichachieves a viscosity of 500 to 900 Pascal-second in 2 to 3 minutes fromthe beginning of mixing and/or which remains sufficiently flowable forinjection for at least 6 to 10 minutes.

In an exemplary embodiment of the invention, higher molecular weightPMMA in the polymer beads cause the mixture to achieve a flowableplastic phase earlier than previously available cements and/or to remainin the flowable plastic phase longer than previously availablealternatives. Optionally, altering the percentage of higher molecularweight PMMA in the polymer beads alters a viscosity profile of theresultant mixture.

Optionally, at least one bead of PMMA has molecular weight in the rangeof 700,000 Dalton to 1,000,000 Dalton. In an exemplary embodiment of theinvention, approximately 3% of the beads have PMMA characterized by amolecular weight in this range.

In an exemplary embodiment of the invention, a setting material isformulated to have a high viscosity for a working window of significantduration, for example, 2, 4, 5, 8, 10 or intermediate or more minutes.

In an exemplary embodiment of the invention, the following formulationis used: a set of beads formed of PMMA/Styrene of diameter 10-200microns and an amount of 20 cc MMA per 9.2 grams beads. In an exemplaryembodiment of the invention, MMA solvates and/or encapsulates the beadsand the viscosity of the mixture remains high, at the beginning due tothe solvation and friction between the beads and later, as the beadsdissolve, due to the progressing of polymerization. The beads may alsobe provided in a mixture comprising a range of sizes. It should be notedthat the properties of the materials may be selected to improve aviscosity working window, even if strength of the final cement iscompromised.

In an exemplary embodiment of the invention, the working viscosity isset by selecting the bead size and/or material ratios and/or molecularweights of polymer provided in the beads.

In an exemplary embodiment of the invention, the working viscosity isinfluenced by the presence of particles of hardened acrylic polymeradded to the mixture.

Mechanical Viscosity Increasing Agents

In an exemplary embodiment of the invention, the cement includesparticles characterized by a large surface which do not participate inthe polymerization reaction. Examples of materials suitable for use asparticles characterized by a large surface are which do not participatein the polymerization reaction include, but are not limited toZirconium, hardened acrylic polymer and bone. Optionally, the particlescharacterized by a large surface which do not participate in thepolymerization reaction are not X-ray transparent so that they aid invisualization of injected cement. In an exemplary embodiment of theinvention, the large surface area particles impart added viscosity tothe cement mixture independent of polymerization. Optionally, the addedviscosity comes from friction of particles against one another in thecement.

Polymerization Reaction Kinetics

In an exemplary embodiment of the invention, mixture of polymer andmonomer components produces a material with a viscosity in the range 500to 900 Pascal-second within 120, optionally within 100, optionallywithin 60, optionally within 30, optionally within 15 seconds or lesseror greater or intermediate times. In an exemplary embodiment of theinvention, once a high viscosity is achieved, the viscosity remainsstable for 5 minutes, optionally 8 minutes, optionally 10 minutes orlesser or intermediate or greater times. In an exemplary embodiment ofthe invention, stable viscosity indicates a change of 10% or less in twominutes and a change of 20% or less in 8 minutes. The time during whichviscosity is stable provides a window of opportunity for performance ofa medical procedure.

Material with a Glass Transition Temperature

In an exemplary embodiment of the invention, a bone cement includes amaterial characterized by a glass transition temperature higher than 37degrees Celsius. Heating such a material above its glass transitiontemperature, weakens the material. The weakening transforms the materialto a dough-like or putty-like state. In an exemplary embodiment of theinvention, the dough-like material is suitable for delivery using adelivery system as disclosed herein. After delivery, the dough cools to37 degrees Celsius and hardens. Examples of materials with a glasstransition temperature above 37 degrees include, but are not limited to,polycaprolactone (PCL) and/or Polylactic acid (PLA). Polymers with glasstransition temperatures suitable for use in the context of the inventionare commercially available, for example “Lactel absorbable polymers”(Curect Corp.; Pelham, Ala., USA).

In an exemplary embodiment of the invention, a material with a glasstransition temperature above 35, optionally 40, optionally 45,optionally 50, optionally 55, optionally 60 degrees Celsius is selected.

Optionally, the delivery system is heated to maintain the material abovethe glass transition temperature. In an exemplary embodiment of theinvention, a heating element is provided in and/or adjacent to thecement reservoir and/or the cannula.

Use of Bone in Bone Cement

In an exemplary embodiment of the invention, the bone cement or otherdough-like material includes processed bone (from human or animalsorigin) and/or synthetic bone. Optionally, the cement hasosteoconductive and/or osteoinductive feature. Optionally, theprocessing of the bone includes grinding. One of ordinary skill in theart will be capable of processing bone using known methods for use inthe context of the present invention.

In an exemplary embodiment of the invention, the bone cement comprises50%, optionally 60% optionally 70% or intermediate or greaterpercentages of bone powder and/or granules and/or chips.

Additional Implant Devices

Optionally, an implant is also injected into the vertebra, for example,before, during or after injection of the material. Exemplary implantsare metal or polymer cage or intra ventricular devices and enclosingmesh or solid bags or balloons. Optionally, bone graft is injected.Optionally, where an implant is provided, the material is extrudedthrough the implant, for example from an axial section thereof in aradial direction.

Optionally, devices such as, for example, those described in PCTapplications PCT/IL00/00458; PCT/IL00/00058; PCT/IL00/00056;PCT/IL00/00055; PCT/IL00/00471; PCT/IL02/00077; PCT/IL03/00052; andPCT/IL2004/000508, PCT/IL2004/000527 and PCT/IL2004/000923, thedisclosures of which are incorporated herein by reference, are used.

Optionally, the material is extruded into a performed cavity, forexample a cavity formed using an inflatable balloon. Optionally, thematerial is extruded into an inter-vertebral space, for example adisc-space.

Optionally, a material which sets to a hardened condition, for example,PMMA is co-extruded with or extruded before or after material which doesnot so set. Optionally, the setting material comprises less than 60% ofthe material, for example, less than 40%, less than 20% or intermediatevalues.

Other Tissue and General

While the above application has focused on the spine, other tissue canbe treated as well, for example, compacted tibia plate and other boneswith compression fractures and for tightening implants, for example, hipimplants or other bone implants that loosened, or during implantation.Optionally, for tightening an existing implant, a small hole is drilledto a location where there is a void in the bone and material is extrudedinto the void.

It should be noted that while the use in bones of the above methods anddevices provide particular advantages for bone and vertebras inparticular, optionally, non-bone tissue is treated, for example,cartilage or soft tissue in need of tightening. Optionally, thedelivered material includes an encapsulated pharmaceutical and is usedas a matrix to slowly release the pharmaceutical over time. Optionally,this is used as a means to provide anti-arthritis drugs to a joint, butforming a void and implanting an eluting material near the joint.

According to various embodiments of the invention, a bone cementaccording to the invention is injected into a bone void as a preventivetherapy and/or as a treatment for a fracture, deformity, deficiency orother abnormality. Optionally, the bone is a vertebral body and/or along bone. In an exemplary embodiment of the invention, the cement isinserted into the medullary canal of a long bone. Optionally, the cementis molded into a rod. In an exemplary embodiment of the invention, therod serves as an intra-medular nail.

It will be appreciated that the above described methods of implantingand treating may be varied in many ways, including, changing the orderof steps, which steps are performed more often and which less often, thearrangement of elements, the type and magnitude of forces applied and/orthe particular shapes used. In particular, various tradeoffs may bedesirable, for example, between applied forces, degree of resistance andforces that can be withstood. Further, the location of various elementsmay be switched, without exceeding the spirit of the disclosure, forexample, the location of the power source. In addition, a multiplicityof various features, both of method and of devices have been described.It should be appreciated that different features may be combined indifferent ways. In particular, not all the features shown above in aparticular embodiment are necessary in every similar exemplaryembodiment of the invention. Further, combinations of the above featuresare also considered to be within the scope of some exemplary embodimentsof the invention. In addition, some of the features of the inventiondescribed herein may be adapted for use with prior art devices, inaccordance with other exemplary embodiments of the invention. Theparticular geometric forms used to illustrate the invention should notbe considered limiting the invention in its broadest aspect to onlythose forms, for example, where a cylindrical tube is shown, in otherembodiments a rectangular tube may be used. Although some limitationsare described only as method or apparatus limitations, the scope of theinvention also includes apparatus programmed and/or designed to carryout the methods.

Also within the scope of the invention are surgical kits which includesets of medical devices suitable for implanting a device or material andsuch a device. Section headers are provided only to assist in navigatingthe application and should not be construed as necessarily limiting thecontents described in a certain section, to that section. Measurementsare provided to serve only as exemplary measurements for particularcases, the exact measurements applied will vary depending on theapplication. When used in the following claims, the terms “comprises”,“comprising”, “includes”, “including” or the like means “including butnot limited to”.

It will be appreciated by a person skilled in the art that the presentinvention is not limited by what has thus far been described. Rather,the scope of the present invention is limited only by the followingclaims.

The invention claimed is:
 1. A bone cement comprising; a first powdercomponent containing polymer beads having a first average molecularweight and further containing a high molecular weight population ofbeads having a second average molecular weight that is higher than thefirst average molecular weight; and a second liquid component containingmonomers, wherein, the first average molecular weight, the secondaverage molecular weight, and the percentage of beads having the secondaverage molecular weight are selected so that contacting the firstcomponent and the second component produces a mixture having a viscosityprofile with three phases defining an initial period a working period,and a hardening period, wherein, during the initial period, theviscosity increases at a rate of change that decreases over time untilthe mixture attains a viscosity greater than 500 Pascal seconds within180 seconds from mixing the first and second components, wherein,during, the working period of at least 5 minutes, the viscosity remainsbetween 500 and 2000 Pascal seconds wherein, during the hardeningperiod, the viscosity increases at a rate of change that increases overtime until the mixture hardens, and wherein the mixture is suitable forin-vivo use.
 2. The bone cement of claim 1, wherein the working periodis at least 8 minutes long.
 3. The bone cement of claim 1, wherein theinitial period is less than 3 minutes.
 4. The bone cement of claim 1,wherein the initial period does not exceed 1 minute.
 5. The hone cementof claim 1, wherein the first component includes PMMA and BariumSulfate.
 6. The bone cement of claim 1, wherein the second componentincludes MMA and DMPT.
 7. The bone cement of claim 1, wherein the firstcomponent includes PMMA, Barium Sulfate, and Benzoyl Peroxide, andwherein the second component includes MMA, DMPT, and Hydroquinone. 8.The bone cement of claim 1, wherein the viscosity of greater than 500Pascal-second results at least partly from a polymerization reaction. 9.A bone cement comprising: a first powder component containing polymerbeads having a first average molecular weight and further containing ahigh molecular weight population of beads having a second averagemolecular weight that is higher than the first average molecular weight;and a second liquid component containing monomers, wherein, the firstaverage molecular weight, the second average molecular weight, and thepercentage of beads having the second average molecular weight areselected so that contacting the first component and the second componentproduces a mixture having a viscosity profile with three phases definingan initial period, a working period, and a hardening period, wherein,during the initial period, the viscosity increases at a rate of changethat decreases over time until the mixture attains a viscosity greaterthan 200 Pascal seconds within 1 minute from mixing the first and secondcomponents, wherein, during the working period of at least 5 minutes,the viscosity of the mixture remains between 200 and 2000 Pascalseconds, wherein the viscosity of said mixture is changing by less than10% in a period of 2 minutes within said working period wherein, duringthe hardening period, the viscosity increases at a rate of change thatincreases over time until the mixture hardens, and wherein the mixtureis suitable for in-vivo use.
 10. The bone cement of claim 9, wherein thethe first component contains PMMA beads and the second componentcontains MMA monomers, the high molecular weight population of PMMAbeads having an average molecular weight between about 600,000 Daltonand about 1,200,000 Dalton.
 11. The bone cement of claim 10, wherein thefirst component contains about 69.4% w/w PMMA, about 30.1% BariumSulfate, and about 0.5% Benzoyl Peroxide; and wherein the secondcomponent contains about 98.5% v/v MMA, about 1.5% DMPT, and about 20ppm Hydroquinone.
 12. The bone cement of claim 10, wherein the firstaverage molecular weight of the PMMA heads is between about 80,000Dalton and about 180,000 Dalton.
 13. The bone cement of claim 10,wherein the first average molecular weight of the PMMA beads is about110,000 Dalton.
 14. The bone cement of claim 10, wherein at least 80% ofthe PMMA beads have a size between 10 and 200 microns.
 15. The bonecement of claim 1, wherein during the initial period, the mixture hassubstantially no liquid phase.
 16. The bone cement of claim 1, whereinduring the initial period, the mixture achieves a viscosity of greaterthan 900 Pascal seconds.
 17. The bone cement of claim 1, wherein thepolymer beads comprise acrylic polymer beads.
 18. The bone cement ofclaim 1, wherein viscosity of t he mixture changes by less than 20% overa period of 5 minutes during the working period.
 19. The bone cement ofclaim 9, wherein the working period is at least 8 minutes long.